The Ottawa Hospital’s Biotherapeutics Manufacturing Centre is building the future of medicine
Making cutting-edge therapies and world-changing vaccines in the most successful facility of its kind in Canada
Our state-of-the-art Biotherapeutics Manufacturing Centre (BMC) is a leader in the rapidly growing field of biotherapeutics — one of the most cutting-edge areas of medical innovation.
We’re using stem cells, cancer-killing viruses, gene therapy, and more, to improve and save lives. We’ve also manufactured more than 15 different cell- and virus-based living drugs for human clinical trials conducted in 11 different countries.
“Biotherapeutics harness the cell’s own machinery — such as proteins, genetic material, and viruses — to address the underlying biological processes that cause disease. Biological therapeutics may be able to cure some diseases.”
We’re the only hospital-based facility in Canada that has widely produced both cell- and virus-based therapies, and in the ongoing global fight against COVID-19, The Ottawa Hospital helped fill Canada’s critical needs in vaccine manufacturing for clinical trials.
The innovations taking place at the BMC are making a real difference in the lives of people right here in Ottawa.
There is no other facility in Canada doing what we do. The BMC offers end-to-end manufacturing solutions to academic and industrial partners around the world, done according to the highest standard of good manufacturing practices. We also founded CanPRIME, the only hands-on biomanufacturing training program in Canada.
As an integral part of Canada’s growing biomanufacturing ecosystem, we’re creating the future of medicine here at The Ottawa Hospital, every day.
FAST FACTS
Opened in 2006
40 highly skilled staff
8 product suites
15+ different cells and viruses manufactured
11 countries where our products have been used
Welcome to The Ottawa Hospital’s Biotherapeurics Manufacturing Centre
Vittorio Petrin has never seen his grandchildren’s faces. The Italian draftsman started to lose his peripheral vision in the early 1980’s after his second son was born, forcing him to leave work and take an early pension. He was diagnosed with retinitis pigmentosa, a genetic disorder that causes the cells in the retina to break down. There is no cure. His vision steadily got worse until he couldn’t see any light at all.
Before his vision went dark, Vittorio spent six years building a model of St. Mark’s Basilica in Venice, using over 3,000 copper pieces. “It was the most beautiful place I’d seen, and I wanted to replicate it. Working on it kept my mind away from what was going to happen,” he says.
Vittorio Petrin with a replica of St. Mark’s Basilica he built while losing his vision to retinitis pigmentosa.
“My dad was an artist. He was able to draw phenomenally, he liked taking videos. Sight was important to him,” says Vittorio’s son Dino Petrin. “He never complained about going blind, we never saw it as children. He always had a sense of humour and a strong character. He never asked for any pity, he just took it in stride.”
Millions of people in North America live with retinal diseases like retinitis pigmentosa, glaucoma, retinal ischemia and age-related macular degeneration. These diseases are poorly understood, progressive, and often untreatable.
But thanks to promising gene and cell therapies in development, Dino hopes that one day people like his father won’t have to lose their vision.
Dr. Catherine Tsilfidis
“Soon we’ll be able to do what our lab has been trying to do all along – bring XIAP gene therapy into the clinic.”
– Dr. Catherine Tsilfidis
A discovery with game-changing potential
Dr. Catherine Tsilfidis can imagine the day when the first patient is treated with the retinal disease gene therapy her lab has worked on for the past 20 years. While it won’t happen tomorrow, that day is not far off.
“XIAP gene therapy is exciting because it keeps cells in the back of the eye from dying,” said Dr. Tsilfidis, a senior scientist at The Ottawa Hospital and associate professor at the University of Ottawa. “It could slow or stop vision loss caused by many different retinal diseases.”
Dr. Tsilfidis is leading a world-class team of researchers that recently received $2.4 M from the Ontario Research Fund to develop gene and cell therapies for retinal diseases. One of their goals is to do the work needed to bring XIAP gene therapy into clinical trials, which could start in the next few years.
The time is right for gene and cell therapy
The promise of replacing defective genes and cells in the eye with healthy ones is undeniable. While these fields are still in their infancy, they are expected to grow exponentially over the next decade. Gene therapy for the eyes has particularly taken off, with Health Canada approval of the first gene therapy for a rare genetic form of vision loss in 2020.
“This research program could make Ontario a leader in the fields of both gene and stem cell therapy
– Dr. Pierre Mattar
When it comes to cell therapies, Ottawa and Toronto are major hubs in the growing area of stem cell research. As partners in the retinal research program led by Dr. Tsilfidis, UHN scientist Dr. Valerie Wallace will work on increasing the survival of transplanted stem cells in the eye, while The Ottawa Hospital’s Dr. Pierre Mattar aims to develop stem cell therapies for retinal ganglion cell diseases such as glaucoma. “This research program could make Ontario a leader in the fields of both gene and stem cell therapy,” said Dr. Mattar. “By learning the best way to mass produce and integrate stem cells for retinal disease, we can advance stem cell research in other fields.”
Dr. Pierre Mattar
Collaboration between lab researchers and clinicians key to success
The incredible challenge of bringing a basic science discovery to clinical trials requires an exceptional team. For this research program, Dr. Tsilfidis assembled a “dream team” of long-time collaborators and new partners.
As a basic scientist, Dr. Tsilfidis has always worked closely with clinicians to help ensure her research reflects patient needs.
“Ophthalmologists help us identify the most important questions to ask,” said Dr. Tsilfidis. “Our lab started working on diseases like Leber hereditary optic neuropathy and glaucoma because clinicians told us how much of a problem they were.”
Two of Dr. Tsilfidis’ long-time clinical collaborators, Drs. Stuart Coupland and Brian Leonard, are part of this new retinal research program. They are joined by retina specialists Drs. Bernard Hurley and Michael Dollin, who will assist in developing clinical trial protocols.
“Our researchers have an incredible track record of taking discoveries from the lab to the bedside,”
– Dr. Duncan Stewart
Dr. Tsilfidis’ lab and office are just down the hall from the ophthalmologists’ offices and clinics, which makes collaboration easier. This kind of co-location of scientists and clinicians has been key to The Ottawa Hospital’s success in translating discoveries from the lab bench to the patient bedside.
Leveraging our biomanufacturing expertise at The Ottawa Hospital
In addition to clinical experts, the team knew they needed new resources and partners to be successful.
“We’ve been very much a basic science lab in the past,” said Dr. Tsilfidis. “Now that we’re at the stage that we want to get XIAP to the clinic, we need all the help we can get.”
One missing piece was a special clinical-grade virus used to deliver the XIAP gene into the eye, known as an adeno-associated virus (AAV). Finding cost-effective sources of AAVs has been a major bottleneck for getting gene therapy trials and treatments off the ground.
Thankfully, The Ottawa Hospital is home to the Biotherapeutics Manufacturing Centre (BMC), a world-class facility that has manufactured more than a dozen different virus- and cell-based products for human clinical trials on four continents. Experts at the BMC were already starting to expand into AAV manufacturing when Dr. Tsilfidis approached them about collaborating on the retinal research program.
The BMC has since been working with Dr. Tsilfidis and her team to develop a process to manufacture the AAVs the team will need for Health Canada approval of the XIAP gene therapy for clinical trials.
The BMC is on track to become the first facility in in Canada to make clinical-grade AAV vectors for gene therapy studies. This new expertise will help them support other gene therapy trials with a focus on rare disease.
Learn more about our Biotherapeutics Manufacturing Centre.
How to plan a world-class clinical trial
In addition to the clinical-grade virus, the retinal research team needed help planning a future clinical trial of XIAP gene therapy. Fortunately, there are no shortage of clinical trial experts at The Ottawa Hospital.
“I’ve never planned a clinical trial before,” said Dr. Tsilfidis “But I knew someone who had – Dr. Dean Fergusson. I’ve always been impressed by the rigorous trails he’s helped develop. When I asked for his advice, he referred me to the Ottawa Methods Centre.”
The Ottawa Methods Centre is The Ottawa Hospital’s one-stop shop for research expertise and support. Their goal is to help all clinicians, staff and researchers at the hospital conduct the highest quality research, using the best methods. They support over 200 research projects a year, led by clinical and basic researchers alike.
“The Ottawa Methods Centre has been amazing to work with,” said Dr. Tsilfidis. “Their research methodology expertise has strengthened this research program and our funding applications.”
Drs. Manoj Lalu and Dean Fergusson along with other experts at the Ottawa Methods Centre are helping to plan a future clinical trial of gene therapy for retinal disease.
At the Ottawa Methods Centre, the team is leveraging the Blueprint Translational Research Group’s Excelerator program, designed to enable efficient translation of basic research discoveries to the clinic through rigorous methods and approaches. Co-led by Dr. Dean Fergusson and Dr. Manoj Lalu, the program will help design the clinical trial protocol, and support the clinical trial application to Health Canada through systematic reviews of available pre-clinical and clinical data.
Research program holds enormous promise
Tackling retinal disease will be a big challenge, but Dr. Tsilfidis has assembled an excellent team of partners both old and new to move this research program forward.
“These therapies could be life-changing. If we could cure or slow down the progression of vision loss, that would be amazing.”
– Dino Petrin
“Our researchers have an incredible track record of taking discoveries from the lab to the bedside, but it can only be done through team efforts like this one,” said Dr. Duncan Stewart, Executive Vice-President of Research at The Ottawa Hospital and professor of medicine at the University of Ottawa. “Fully leveraging our basic and clinical expertise, as well as our world-class core research resources is the key to getting new treatments to the patients who need them.”
For Dr. Tsilfidis, the excitement is palpable. “Soon we’ll be able to do what our lab has been trying to do all along – bring XIAP gene therapy into the clinic.”
Dino, a former graduate student in Dr. Tsilfidis’ lab, sees the potential of gene therapies to help people like his father. “These therapies could be life-changing,” he said, “If we could cure or slow down the progression of vision loss, that would be amazing.”
Vittorio Petrin with his wife Maria Petrin
The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.
Categories: Innovation and Technology, Stem Cell, Technology, World-Leading Research
Originally published: January, 2022
When Owen Snider faced the news that his lymphoma had returned for the third time in ten years, he knew his options were running out. But a transformational new treatment known as CAR-T therapy gave him renewed hope. The Ottawa Hospital was recruiting patients for a clinical trial investigating a made-in-Canada approach to this cutting-edge treatment. He just needed to qualify for the trial.
In 2010, Owen was diagnosed with large B-cell lymphoma. In his early 60s at the time, he went through a chemotherapy treatment known as R-CHOP. For most people, it lasts 18 weeks. “It was a rigorous treatment. I got through it okay and was six years clear, but then it came back — the lymphoma returned in 2016,” says Owen.
When the cancer returned, his care team at The Ottawa Hospital vetted him for a stem cell transplant. By the summer of that year, he went through what he called an intensive program using his own stem cells. A high dose of chemotherapy was used to remove harmful immune cells in preparation for the transplant of his own healthy cells. “It’s pretty brutal, and after two or three months of wishing maybe I wasn’t around, things improved. I was clear for another four years.”
“I was given five or six months to live. My wife and I were downhearted with that news.”
— Owen Snider
Lymphoma returns for a third time
Following his stem cell transplant, Owen remained healthy for four years, enjoying retirement at his home in a beautiful, wooded area near Calabogie, where he lives with his wife, Judith Snider. But then Owen faced his biggest challenge yet when the lymphoma returned — again. This time, the diagnosis came in May 2020, in the midst of the pandemic. “I remember my oncologist saying they’ve done pretty much everything they could. I was given five or six months to live. My wife and I were downhearted with that news. I was basically going to be kept as comfortable as possible for six months,” remembers Owen.
Judith and Owen Snider kayaking.
However, one week later Owen received a lifeline. His oncologist called to say a CAR-T therapy clinical trial had opened at The Ottawa Hospital — a Canadian first. They wanted to see if he would be a good candidate. Throughout June of 2020, he went through a battery of tests and scans to see if he qualified for the trial.
“This type of immunotherapy research is groundbreaking, and it’s never been done in Canada before.”
– Dr. Natasha Kekre
By mid-June, Owen got the green light. He was a candidate for the clinical trial, and didn’t hesitate to enroll. “I either participate in the trial or I lie around here for four or five months waiting for the end. Which choice would you have made? The positive way to put it is that I was very excited to be a part of the trial. We’re the kind of people where the glass is always half-full,” explains Owen.
CAR T-cell therapy is a type of immune therapy that is an emerging biotherapeutic treatment that harnesses the power of a patient’s own immune cells, known as T-cells, to treat their cancer. T-cells play a critical role by killing abnormal cells, such as cells infected by germs or cancer cells. In some cancers, like lymphoma or leukemia, cancerous cells become invisible to the T-cells that are meant to kill them. In CAR-T therapy, the T-cells are collected and reprogrammed in the lab to recognize and destroy the cancerous cells.
Dr. Natasha Kekre is a hematologist and associate scientist at The Ottawa Hospital. She is leading the development of Canada’s first CAR-T research platform in collaboration with the BC Cancer Centre. “This type of immunotherapy research is groundbreaking, and it’s never been done in Canada before. This is a therapy that uses a patient’s own immune system. It’s personalized medicine — it’s very individualized to each patient,” explains Dr. Kekre.
The Ottawa Hospital is one of the first hospitals in Canada to participate in nationally-led CAR-T trials, and as one of Canada’s top research and treatment centres, the hospital is ideally positioned to play a lead role in bringing an innovative CAR-T research program to Canada, and to Canadian patients.
Going for the Pac-Man effect
In late June 2020, Owen went through apheresis which is the process of withdrawing the T-cells in his blood. “They put an IV in my right arm, and ran the tubing through the machine, and the machine processes the blood and pumps it back through the tubing into my other arm. I lay there on the bed for three or four hours, without moving I should add.”
“It’s just like Pac-Man, the modified T-cells ran around in my blood stream, chomping away at the lymphoma.”
– Owen Snider
Those T-cells were then sent to a lab in BC, re-programmed, and then returned to our hospital two weeks later. Then the T-cells were re-administered just like a blood transfusion. “It allows for that new immune therapy in these cells to go and find the patient’s cancer cells, attack them, and kill them. And it also stimulates the immune system in that patient to further go attack and fight their cancer,” explains Dr. Kekre.
On July 2, Owen received a PICC line and then went through three days of chemotherapy. Four days later he was re-injected with his T-cells and they got to work. “It’s just like Pac-Man, the modified T-cells ran around in my bloodstream, chomping away at the lymphoma.”
His re-programmed T-cells were specifically looking for cancer cells to kill. Owen would need to wait to find out if it was working.
Owen Snider
Did the CAR T-cells therapy work?
One month later, Owen and Judith received some exceptional news. “At my check-up 30 days after getting my T-cells back, I was almost clear of cancer. The scan showed that there was almost nothing left. I was gobsmacked,” he says.
By the three-month mark, Owen says he was as “clean as a whistle.” Eighteen months later, there is still no sign of lymphoma.
For Dr. Kekre, giving patients like Owen new hope for the future is what inspires her. “For the first time, I think in a long time, Owen felt that the lymphoma might actually be disappearing. He’s had multiple scans since then that show the same thing. And so now, I think he’s starting to believe it. And I think that’s the reality of why I do this, because patients like him who had no options before, could soon have the option of CAR-T therapy. That’s what happened for Owen and that’s what we hope will happen for many more patients,” says Dr. Kekre.
Dr. Natasha Kekre and Owen Snider. Owen was treated for lymphoma as part of a CAR-T clinical trial.
What’s next for the clinical trial?
Dr. Kekre and her team are monitoring all patients enrolled in the trial and published preliminary results in June 2022. The purpose of the clinical trial is to provide proof to Health Canada this therapy is safe. “The reality is that we have a data safety monitoring board, which watches for the safety of the trial, and they’ve had no concerns. So, from a safety point of view, we’re very happy with the trial. And that’s why we are still open and we’re still able to enroll more patients,” explains Dr. Kekre.
Why is The Ottawa Hospital unique in its CAR-T therapy?
CAR-T therapy needs to be individually manufactured for each patient using the patient’s own cells combined with large amounts of highly pure virus to deliver the chimeric antigen receptors (CAR) gene. The Ottawa Hospital’s Biotherapeutics Manufacturing Centre is ideally positioned to manufacture the clinical grade virus needed to create CAR T-cells for clinical trials. In fact, we have the only facility in Canada that has produced this kind of virus for clinical trials.
The hope is that one-day CAR T-cell therapy may also be a treatment for a variety of cancers. “The world is watching us,” explains Dr. Kekre. “We’ve had a lot of attention from Denmark, and a few other European countries are reaching out. They believe in a system similar to ours, where patients all have the right to access healthcare. If CAR T-cells are here to stay, they have to be done in a sustainable approach for our patients. And that’s a big part of what we are building — this is only the beginning. And that’s what people are looking at us to see how we do it.”
“Without philanthropy, we wouldn’t have a Biotherapeutics Manufacturing Centre or a Methods Centre at The Ottawa Hospital, and we wouldn’t be able to do innovative clinical trials like this.”
– Dr. Natasha Kekre
This made-in-Canada CAR T-cell research platform will give Canadian patients more access to innovative clinical trials. “Canadian cancer patients shouldn’t have to wait for the research to be done elsewhere but be able to participate in innovative clinical trials here at home,” says Dr. Kekre.
Grateful for each day and philanthropic support for research
Today, Owen appreciates each day and a good quality of life thanks to the clinical trial. He feels strong and can’t wait for the day when he and Judith can travel again — grateful for the lifesaving research. “It was an honour and a privilege to be chosen for the trial.”
He also credits the extraordinary care team and those special moments when he visited the hospital. “I can tell you that I always felt more than comfortable. I felt encouraged by anyone I met. The team on 5 West as we know it, is wonderful. I had an occasion to go back there last spring, and it was like walking back into Cheers — everybody knows your name.”
As a longtime supporter of The Ottawa Hospital, and to see philanthropy play an important role in making this clinical trial a reality, he’s an even bigger advocate for encouraging support for our hospital. “All I can say is that the core funding of hospitals doesn’t provide for some of the innovative and cutting-edge things that go on, or maybe some really specialized piece of equipment. And that’s where the community donor can help and contribute to that effort.”
Owen and Judith Snider.
For Dr. Kekre, philanthropy provides the spark for clinical trials like this, and can help to keep them moving forward. “Without philanthropy, we wouldn’t have a Biotherapeutics Manufacturing Centre or a Methods Centre at The Ottawa Hospital, and we wouldn’t be able to do innovative clinical trials like this. We need this kind of research to get to a place where all Canadians can benefit from these therapies. Without philanthropy, we would never get there.”
And to Dr. Kekre, her team, and their collective efforts to give more patients hope, Owen has a simple message: “Thank you. The whole program is outstanding.”
About the Canadian-Led Immunotherapies in Cancer (CLIC) research program
The CLIC research program, established in 2016, brings researchers, clinicians and patients from across Canada together to build Canadian expertise and capacity for innovation in the promising field of cellular immunotherapy for cancer, including CAR-T therapy. The first CLIC clinical trial launched in 2019 at The Ottawa Hospital and at BC Cancer, with support from BioCanRx, BC Cancer, The Ottawa Hospital Foundation and the Ontario Institute for Cancer Research. Core facilities and resources supporting CLIC include The Ottawa Hospital’s Biotherapeutics Manufacturing Centre, BC Cancer’s Conconi Family Immunotherapy Lab, the Ottawa Methods Centre and the Blueprint Translational Research Group. CLIC team investigators include Drs. Natasha Kekre, Harold Atkins, John Bell, Kevin Hay, Rob Holt, Brad Nelson, John Webb, Manoj Lalu, Kednapa Thavorn, Dean Fergusson, Justin Presseau and Jen Quizi.
The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.
Categories: Cancer, Cancer, Clinical Trials, Clinical Trials, Innovation and Technology, Patient Care, World-Leading Research, World-Leading Research, World-Leading Research, World-Leading Research, World-Leading Research, World-Leading Research, World-Leading Research
When COVID-19 moved into the Ottawa region in March of 2020, we were in uncharted territory. However, despite the rapidly changing information in the early days, and the unknowns about this virus, something very clear began to emerge – unity. The community would soon show an outpouring of support for The Ottawa Hospital while healthcare teams rallied together to care for patients.
“Thank you to our generous donors – some who reached out for the first time.” – Tim Kluke
As our front-line workers would go into the hospital each day to face the virus head-on, the community stayed home to help flatten the curve. Nevertheless, it became obvious residents wanted to do more – and they did. Donations both big and small began streaming in and the COVID-19 Emergency Response Fund was created. To date, more than $2 million has been generously donated to support our hospital’s COVID-19 efforts and these donations have already been put to work. Tim Kluke, President and CEO of The Ottawa Hospital Foundation, says this support has made a world of a difference supporting both research and care projects. “This proves once again that we really are stronger when we pull together. Thank you to our generous donors – some of whom have even reached out for the first time. Research currently underway will allow us to better understand and treat the virus, to keep our patients and our community safe.” Donations continue to be accepted today.
Personal Protective Equipment (PPE) was another way our community lent a helping hand. The Ottawa Chinese Community quickly mobilized and raised over $120,000 to purchase necessary equipment like ventilators and PPE for our staff.
In Their Own Words: Good Days, Bad Days, and What Keeps Them Coming Back
Stepping into the unknown
While the community united to show their support for our front-line workers, a COVID-19 floor was created at both the General and Civic Campuses to care for the patients who tested positive for the virus. The team at the General Campus that had originally cared for Thoracic, ENT (Ear, Nose, and Throat), and surgical patients would, almost overnight, become the team caring for COVID-19 patients. Little did they know at the time, they would be caring for these patients for well over a year. “We have a background in lungs and breathing issues on our unit, so we were a natural fit to care for these patients,” says Vanessa Large, a registered nurse at our hospital for the past four years.
Vanessa Large, Kristine Belmore, and Leah Mills worked on the “COVID floor” in 2020. Pictured above wearing personal protective equipment (Image 1) and without (Image 2).
Nevertheless, it was a daunting and draining task. Kristine Belmore is a registered nurse who has been at our hospital for 11 years and never did she imagine her career taking this step. “I was working the day the first positive patients came in. We were constantly getting new updates on protocols for caring for these patients – not just daily but during our shifts,” says Belmore. She adds, “It was the equivalent of how I felt when I was a new nurse preparing for a shift — I didn’t sleep well. I was anxious and there was the fear of the unknown.”
Leah Mills was just three years into her career as a registered nurse when she found herself caring for COVID-19 patients. “There was no easing into the COVID transition; it turned our world upside down,” says Leah.
Resilience as weeks turn into months
Dr. Samantha Halman helps a patient communicate with their loved ones via an iPad.
In those early weeks of caring for patients, there was the struggle of watching some patients go from appearing stable to suddenly clinging to life. Those days would take an emotional toll on these nurses. “The increase in demand during the surge of patients was overwhelming. Over time it became easier because we had concrete policies in place and we started recognizing a pattern in patient’s decline,” recalls Leah.
“We became their only sources of human connection, we became their second family. We would be there holding an iPad so they could see the friendly smile of a loved one – sometimes it was to say goodbye.” – Vanessa Large
The playbook had to be reinvented and new ideas had to be considered to help calm patients when they struggled to breathe or feared what might happen next. Then there were the layers of PPE, which created an additional level of safety but also a new challenge. “Caring for patients, especially the elderly who can be confused, was difficult because they can’t see your facial expressions – we had to find new ways to reassure patients when they were scared. We also became the link between the patient and the family, through phone calls and video calls – something we’ve never done before,” says Kristine.
Vanessa agrees adding, “We became their only sources of human connection, we became their second family. We would be there holding an iPad so they could see the friendly smile of a loved one – sometimes it was to say goodbye.”
Mentally and emotionally, the long haul of this pandemic started to wear on these nurses. Leah explains they’re used to helping patients heal and get better. “We’re feeling burned out and exhausted seeing patients decline quickly and sometimes die. It’s not what I’ve been used to in my role.”
Thankfully, over the past year, this dedicated care team has helped ensure the majority of COVID-19 patients have been able to regain their health and return home to their loved ones.
The nurses of the “COVID floor”
“Working on the COVID-19 Unit, with the numbers going up and down, you never know which point is going to be the tipping point.” — Leah
“The best part about starting on the COVID-19 Unit was the team. Everyone was very supportive, willing to teach the newbies on the unit. And, the patients especially, they were very accommodating, and I will remember them for a long time to come.” — Margaret
“My worst part of this year was seeing a lot of suffering and not being able to help as much as I would want to.” — Michael
“COVID-19 has taught me to really value and cherish the time that I had with my family, my friends, and my colleagues.” — Jeannette
COVID-19 patient grateful for compassionate care
One of the patients, who experienced firsthand compassionate care on the COVID-19 floor, was Fr. Alex Michalopulos. The Greek Orthodox priest spent 10 days in our hospital. He couldn’t be more thankful to be feeling better today. “For the times when the doctors or nurses came in to see me, for the times when I was reassured—I’m thankful I was well taken care of with love and respect for human life.”
“I have a lot more respect for the medical professionals. I always had, but this time it was at a different level. They were there for me.” – Fr. Alex Michalopulos
Father Alex Michalopoulos of the Greek Orthodox Church. Father Alex was treated for COVID-19 at The Ottawa Hospital last year.
As tears well up in his eyes, and he stops briefly to regain his emotions, Fr. Michalopulos says it’s sometimes good to be on the other side, to feel what others are going through. “I have a lot more respect for the medical professionals. I always had, but this time it was at a different level. They were there for me.”
He adds, “They held my hand. They showed compassion. They showed a lot of respect and love. I will be forever grateful for them.” It was that special touch, and care from complete strangers that helped give Fr. Michalopulos the strength to get back home to the family he loves and eventually to his parish family.
“I will always remember how I was treated by strangers. I admire them and will always pray for them.”
In an effort to do his part to help, Fr. Michalopulos is participating in research that is investigating the long-term effects of the virus. Drs. Sara J. Abdallah and Juthaporn Cowan are checking in on participating patients, like Fr. Michalopulos at three, six, and 12 months after they were initially infected.
He explains why it was important to become involved. “I thought it would be useful to help researchers understand the effects and lingering effects of the virus in gathering information to help create a vaccine and or a cure.”
Giving back through research
Researchers at our hospital have been deeply involved in the global race to combat COVID-19. They are exploring more than 60 research projects to support the worldwide effort to find better ways to treat and prevent the virus. A number of those projects have been supported by donors through the COVID-19 Emergency Response Fund, including a world-first clinical trial, led by Dr. Rebecca Auer, which aims to protect cancer patients from COVID-19 – to date, 22 patients, have been recruited.
Dr. John Bell is a senior scientist in the cancer therapeutics program at The Ottawa Hospital.
Dr. Carolina Ilkow is a scientist in the cancer therapeutics program at The Ottawa Hospital.
Drs. John Bell and Carolina Ilkow are harnessing their expertise in making cancer-fighting viruses to develop a vaccine against COVID-19 — a made-in-Canada solution. In addition, our Biotherapeutics Manufacturing Centre is helping to manufacture three other COVID vaccines for clinical trials, as well as an experimental stem cell therapy.
Pushing forward despite a challenging year
As research continues to produce more answers and vaccines continue to roll out across the region, the team caring for patients remains steadfast. “The vaccine brings us hope. I remember how exciting it was when I received mine,” says Kristine.
Venus Lucero, a nurse at The Ottawa Hospital, administers the hospital’s first dose of the COVID vaccine.
There is hope someday they can start getting back to the way things used to be, or at least close to it. For Kristine, it would mean not worrying about hugging her children when she comes home from work.
For Leah, it would mean letting her mind shut off for the first time in a year – and truly relax. For Vanessa, it would mean the excitement of spending time with her fiancé, Colin – also a frontline worker – as they’ve been isolated from each other during the pandemic. Despite the challenges, each one takes great pride in the care they’ve been able to provide during these unprecedented times. And how they also helped each other along the way.
As our researchers move new research projects forward faster than ever in an effort to address COVID-19, donations to the COVID-19 Emergency Response Fund continue to provide seed funding to get these vital projects off the ground. Below are some of the new and promising projects approved for support through the second round of funding. Kick-starting these projects would not have been possible without the support of our generous donors — thank you!
Harnessing cancer-fighting viruses to develop a COVID-19 vaccine
Dr. John Bell
Drs. Carolina Ilkow, John Bell and colleagues are harnessing their expertise in making oncolytic (cancer-fighting) viruses to develop a vaccine against COVID-19, in partnership with scientists and clinicians in Canada and around the world. One of the key things they’ve learned is that the best cancer-killing viruses also stimulate the body’s own immune system – in effect, training the immune cells to recognize and help attack the cancer cells.
They have developed a number of viruses that are very good at boosting the immune system and have already been tested safely in people. These viruses will be reengineered by splicing in key genes from the COVID-19 virus to create several candidate vaccines, which would train the body to mount an immune response against COVID-19. They expect this live vaccine will be particularly important for healthcare workers and vulnerable populations, including people with cancer. Once the vaccine is created, large quantities can be made in The Ottawa Hospital’s Biotherapeutics Manufacturing Centre.
Dr. Carolina Ilkow
“We know that people with cancer who get COVID-19 are much more likely to get severely ill, so we think that working on a vaccine is the best thing we can do right now to help cancer patients.”
– Dr. John Bell
UPDATE: The research team has developed candidate vaccines and laboratory testing is going well. With funding, the team will be ready to do human clinical trials in the new year.
Creating a new mouse model to study COVID-19 lung disease
Dr. Manoj Lalu
Drs. Manoj Lalu, Duncan Stewart and colleagues are working to develop a mouse model of COVID-19 that mimics the severe lung disease seen in humans.
The lack of good, accessible animal models of this disease is severely limiting research around the world. The COVID-19 virus doesn’t infect regular lab mice very well, and the virus is dangerous to work with because it is so contagious for humans.
Drs. Lalu are Stewart are working with Drs. Carolina Ilkow and John Bell, who are creating a novel hybrid virus that features a key protein from the COVID-19 virus (the spike protein) embedded into a well-studied and safe virus called vesicular stomatitis virus (VSV).
The team will test this hybrid virus in mice that have been genetically engineered to be more susceptible to COVID-19, to mimic the severe lung disease seen in humans.
Dr. Duncan Stewart
To make sure the model is accurate, they will use sophisticated techniques to compare their findings in mice with findings from patients, focusing on effects on the lungs, blood and blood vessels. They will then use this model to test new therapies, including mesenchymal stromal cells.
UPDATE: A novel hybrid virus (VSV-Cov2-S) has been manufactured by Dr. Ilkow’s lab with high quality and concentration to proceed with testing in our mouse model. Our experts have worked with the uOttawa Animal Care Committee and have successfully obtained ethics approval. Researchers began challenging ACE2 transgenic mice with the virus in December, controlling for time and dose, and assessing lung injury outcomes.
Studying the immune response of COVID-19 patients in the ICU
Dr. Shirley Mei
Why do some people get severely ill and die of COVID-19, while others experience only mild symptoms? Part of the answer may lie in how an individual’s immune system reacts (and sometimes over-reacts) to the COVID-19 virus. Dr. Shirley Mei and her intensive care research colleagues will study this in critically ill COVID-19 patients using the world’s most advanced “single-cell proteomics” technology.
This technology, called CyTOF, will allow the researchers to study up to 60 different biological factors all at the same time from one single cell. The researchers will create a multi-dimensional map of the immune response to COVID-19, showing how it changes over time and how it sometimes goes out of control.
The data will be shared with clinicians and researchers around the world, in order to improve treatment of COVID-19 and save lives.
UPDATE: Patients participating in this research study will have blood samples taken for a period of 15 days after their enrollment and consent to participate. With approval from the research ethical board, researchers are in the process of recruiting patients into four arms of our study: septic patients in ICU (control cohort), COVID-19 patients in ward (mild disease cohort), ICU patients with severe COVID-19 (severe disease cohort), as well as healthy volunteer (healthy cohort). To date, 34 patients have been recruited with a total of 147 blood samples collected. Pilot experiments to validate the customized immune profiling panel for the mass cytometry (CyTOF) experiment have been completed. This approach will allow researchers to assess the disease progression by using the world’s most advance single-cell proteomics technology.
A balancing act: how to provide regular patient care amid the threat of COVID-19
Dr. Kednapa Thavorn
Dr. Kednapa Thavorn and colleagues will use health administrative data from across Ontario, available through IC/ES, to model the risks of various scenarios for restarting routine clinical procedures in hospitals. Ontario hospitals have postponed many routine clinical procedures in order to preserve resources for COVID-19 patients, but these routine procedures can’t be postponed forever without serious health consequences.
As hospitals contemplate re-staring some routine care, a careful balance will need to be struck between the risks of COVID-19 and the risks of all other preventable diseases and conditions. The model will estimate overall deaths, healthcare costs and other factors for several scenarios, in order to help hospital administrators and policy makers make evidence-based decisions. The model could be adapted for different regions and for different COVID-19 scenarios, including a possible second wave.
UPDATE: Researchers working on this project have developed a detailed protocol of the study and a model structure for a resource optimization model. They have requested the hospital data required for the model and expect to receive this information in January.
Helping COVID-19 survivors stay healthy
Drs. Sara J. Abdallah and Juthaporn Cowan
Drs. Sara J. Abdallah, Juthaporn Cowan and colleagues will study the long-term effects of COVID-19 in survivors, checking in on them three, six and 12 months after they were initially infected. While researchers are beginning to understand what happens in the body during a severe COVID-19 infection, much less is known about the long-term effects in survivors. But based on what is known about other viral infections, the long-term effects could be serious, affecting the lungs, heart and muscles, as well as mental health. Survivors of mild, moderate and severe infections will be included in the study. The researchers will also assess the healthcare resources used by survivors. Results will help improve care for COVID-19 survivors and optimize how healthcare resources are used.
UPDATE: With support from The Ottawa Hospital COVID-19 Emergency Response Fund, researchers set out to understand the medium and long-term impact of COVID-19 on overall health. As of October 31, 2020, 64 enrolled participants completed comprehensive cardiopulmonary testing and important progress has been made in understanding the residual effects of COVID-19 on heart and lung function. As patients continue to be monitored at six and 12-months after COVID-19 infection, our researchers hope that their findings will inform future management strategies for post-COVID breathlessness.
World-first clinical trial aims to protect cancer patients from COVID-19
Dr. Rebecca Auer speaks with a colleague (Photo taken before COVID-19)
Surgeon-scientist Dr. Rebecca Auer is leading a world-first clinical trial that she hopes will protect cancer patients from COVID-19 and other respiratory infections by boosting their immune systems during treatment.
In collaboration with scientists at the Ontario Institute of Cancer Research, researchers will explore an immune-stimulator called IMM-101. The trial will be designed and run by the Canadian Cancer Trials Group at Queen’s University at nine cancer centres across Canada and will recruit 1,500 patients currently receiving cancer treatment.
This trial takes advantage of a lesser-known aspect of the immune system — innate immunity. This first-response arm of the immune system plays a key role in detecting viruses. The research team hopes the IMM-101 treatment will train the patient’s innate immune system to fight off the COVID-19 virus, in addition to other viruses that cause respiratory infections.
The advantage of this immune-boosting approach is that it could help cancer patients fight off all sorts of viruses while they are undergoing cancer treatments and are at their most vulnerable.
The trial has been approved by Health Canada and will run this summer and into the fall. Researchers expect to see preliminary results in about nine months.
UPDATE: The clinical trial was activated in September and is now open in Ottawa for recruitment. The trial will enroll 1,500 patients across Canada, with approximately 200 patients from Ottawa. These Ottawa patients will be part of the translational study funded in part by the COVID-19 Emergency Response Fund.
“While there are many specific vaccines for COVID-19 in the works, they won’t be available for at least a year. Cancer patients need protection now.”
– Dr. Rebecca Auer
The COVID-19 research taking place at The Ottawa Hospital has the potential to transform our understanding of this virus and lead to new ways to prevent and treat it and save lives. This vital research is possible thanks to support from the community. Please consider giving today in support of the COVID-19 Emergency Response Fund.
To find out more about our COVID-19 research and the many collaborators working to make these projects happen, please visit The Ottawa Hospital’s Research Institute.
Keep checking back for more updates on how donations are being put to work right away and are making a difference in The Ottawa Hospital’s fight against COVID-19. To get regular updates sent directly to your inbox, sign up for our newsletter, Vital Links.
The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.
Categories: COVID-19, COVID-19
As the COVID-19 pandemic continues to evolve, experts at The Ottawa Hospital and healthcare partners throughout the region have geared up to stop the spread of this infectious disease. From our crisis preparedness plan, to COVID-19 research already underway, we have the knowledge and experience to tackle this pandemic head-on. Our researchers are harnessing their unique expertise and exploring more than 50 COVID-19 research projects to help in the global fight against this virus.
All of the COVID-19 simulation exercises and research projects being explored at The Ottawa Hospital will make use of shared research equipment, resources, and facilities that have been developed over many years, thanks to generous support from our community.
“Thanks to generous support from the community over the years, we’ve been able to develop unique research facilities and technologies that we are now rapidly applying to the fight against COVID-19,” said Dr. Duncan Stewart, Executive VP Research, The Ottawa Hospital. “Similarly, today’s community support for research means we will be ready for tomorrow’s health challenges, whatever they may be.”
Calming the immune system in critically ill patients
Dr. Stewart is leading a team of researchers working to launch a clinical trial of mesenchymal stromal cells (MSC) therapy for COVID-19 patients with Acute Respiratory Distress Syndrome (ARDS).
The immune system plays a crucial role in defending the body against COVID-19, but sometimes it can become overactivated, resulting in severe damage to the lungs, called ARDS. In COVID-19 patients, ARDS is the major cause of severe illness and death.
Studies have shown that mesenchymal stromal cells (MSCs) can dampen an overactive immune response and help patients with ARDS related to other kinds of infections. Our researchers will build on their extensive experience in manufacturing MSCs and leading the world’s first clinical trial of MSCs for septic shock. This project will likely involve partners in Ontario and Europe, working in a concerted effort to find novel therapies to improve outcomes in COVID-19 patients.
Repurposing existing drugs and finding new ones
Dr. John Bell in his lab at The Ottawa Hospital. His team could use their virus manufacturing expertise in the production of a vaccine for COVID-19.
Other researchers of The Ottawa Hospital and the University of Ottawa are looking to identify already-existing drugs and their potential effectiveness in treating patients with COVID-19. Drs. Taha Azad, Ragunath Singaravelu, Jean-Simon Diallo and John Bell have developed a novel system known as a bio-sensor that can identify small molecule drugs that block the COVID-19 virus from attaching to cells, thereby preventing infection. First, they plan to test this approach on a library of more than 1,000 small molecules that have been approved to treat other diseases. They will then attempt to identify antiviral drugs that could be effective in treating this virus.
Learning from our COVID-19 patients and testing therapies
Researchers from around the world are sharing their experiences and findings and are working together to determine the best approach to treating patients with COVID-19.
To help with this global effort, infectious disease researchers at The Ottawa Hospital and the University of Ottawa are working locally to create a registry of COVID-19 patients in our community. Under the leadership of Dr. Michaeline McGuinty and Dr. William Cameron, the researchers plan to look for patterns among cases and determine how well treatments are working. They will also use blood samples to study the virus and the body’s response to each treatment.
“Thanks to generous support from the community over the years, we’ve been able to develop unique research facilities and technologies that we are now rapidly applying to the fight against COVID-19.” – Dr. Duncan Stewart, Executive VP Research, The Ottawa Hospital
Working towards a vaccine
While some researchers work to find better treatment options for COVID-19, Dr. Carolina Ilkow, Dr. John Bell and their team of experts in making cancer-fighting viruses at The Ottawa Hospital are working hard to develop a possible vaccine, in partnership with scientists and clinicians in Canada and around the world. The vaccine would contain small parts of genetic material from the COVID-19 virus, embedded into a different virus that does not cause human disease. This replicating viral vaccine would also produce its own adjuvant – a substance that stimulates a stronger immune response, resulting in a more effective vaccine. Once a promising vaccine is created, the team will be able to make large quantities in The Ottawa Hospital’s Biotherapeutics Manufacturing Centre. This facility is the only hospital-based lab in Canada capable of producing virus-based vaccines and therapies for clinical trials.
Nurses at the COVID-19 Assessment Centre prepare a swab to be transported to the lab and tested for COVID-19.
Putting preparedness to the test
While our researchers have been nimble in responding to COVID-19 The Ottawa Hospital was already planning for the possibility of a future pandemic long before this virus appeared. When it comes to preparing for the worst, we are leading the way in developing strategies to effectively manage a crisis.
The intensive care units (ICU) at both the General and Civic campuses, where the most acutely ill COVID-19 patients will be treated, will triple their current size should we need the room. If these become over capacitated, the hospital would make use of other existing hospital facilities to increase its ability to care for severely ill patients.
Eastern Ontario hospitals are also working together to create a regional patient flow strategy to care for patients. Hospitals will transfer COVID-19 positive patients who need acute or critical care to select hospitals for treatment. Patients who do not require this level of care will be transferred out of acute or critical care hospitals to the most appropriate hospital setting. This will ensure that our healthcare system does not become overwhelmed by the COVID-19 outbreak.
Simulation exercises save lives
Transferring patients from the Emergency Department to the ICU is no easy feat in a 100-year-old hospital. It’s for this reason, the University of Ottawa Skills and Simulation Centre have readied staff by running simulation drills and tests.
The drills, which made use of a high-tech mannequin capable of sneezing, are designed to refine the safe treatment and transport of a severely-ill patient experiencing respiratory failure.
Simulations are vital as they allow staff to practice their skills in a real-time environment make adjustments if necessary, and ultimately provide better care to patients. Similar to the Code Orange simulations, which took place two months before the Westboro bus crash on January 11, 2019, this type of hands-on training further prepares staff on the frontlines.
On November 16, 2018, The Ottawa Hospital underwent a Code Orange emergency response exercise as part of ongoing preparedness to respond effectively to a disaster in the community. Participating in such a training exercise meant staff would be even more prepared should a real Code Orange be called.
Just two months later, a double-decker bus crashed into the Westboro bus station. Thirteen severely-injured patients were subsequently transported to the Emergency Department. The simulation exercise helped to ensure that The Ottawa Hospital staff were even more prepared to save their lives.
Community support essential
A strong hospital requires the support of its community and that couldn’t be more true than during these unprecedented times. You can support world-class care and ground-breaking research that is saving lives every day.
The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.
Categories: TOH Family
Update: In early 2023, Dr. Thébaud’s team treated the first baby in their clinical trial that aims to prevent BPD in premature infants. This is the first trial of its kind in in the world. Read Dr. Thébaud’s Q&A to learn more about his critical work and what motivates him.
Published: August 2020
Little Olivia Eberts had oxygen tubes in her nose until after her first birthday. Because she was born prematurely, her tiny lungs were underdeveloped, and she couldn’t breathe without oxygen. Ironically for Olivia, and many premature babies like her, the oxygen that saved her life also damaged her lungs, causing bronchopulmonary dysplasia (BPD), which is like starting out life with emphysema. But a clinical trial at The Ottawa Hospital led by Dr. Bernard Thébaud, which uses stem cells to heal the lungs of premature babies, may be a game changer.
An unexpected early birth
Jamie Eberts was 22 weeks pregnant with twins when she started feeling some discomfort. She arrived at the General Campus of The Ottawa Hospital and was admitted — she was going into early labour.
Thankfully, the doctors and nurses at The Ottawa Hospital were ready for any scenario Jamie, her husband Tim, and the babies faced. Each day, there were gentle conversations about how the babies were doing, the process of delivering them, and the chances of survival. Every hour counted. Then, one of the babies developed an infection and all three lives were at risk — the babies had to be delivered.
Baby Olivia in the neonatal intensive care unit (NICU).
“Our babies, Liam and Olivia, were born at 5 a.m. on January 29, 2017, at 23-and-half-week’s gestation. Liam was born first. He was small, red, and didn’t make a sound,” remembers Jamie. Olivia weighed one pound, two ounces and Liam weighed only a few ounces more than she did. Both babies required oxygen and mechanical ventilation to keep them alive. As a result, both developed BPD — the most common cause of death in premature babies.
Sadly, baby Liam passed away a few weeks after he was born while Olivia remained in the Neonatal Intensive Care Unit (NICU) at The Ottawa Hospital for nine long months.
BPD in Canada
Jamie Eberts carrying baby Olivia.
In Canada, 1,000 babies are diagnosed with BPD every year. Often, babies with BPD develop other chronic lung diseases, such as asthma, and many require prolonged oxygen and ventilation. Additionally, they have a high incidence of hospital readmissions in the first two years of life. Babies with BPD often have problems in other organs as well, such as the brain or the eyes.
When Olivia was finally discharged, she went home with an oxygen tank. During the first year of her life, Olivia spent more time in hospital than out.
“Even now, a simple flu that put me in bed for a couple of days put her in hospital and turns into pneumonia. It’s scary,” says Jamie. The doctor told her that with Olivia’s respiratory issues, she may require hospital intervention for the rest of her life.
Lack of treatment options
“Currently there is no treatment for this disease,” says Dr. Bernard Thébaud, a neonatologist and senior scientist at The Ottawa Hospital. With that being said, he’s determined to improve the outcome for babies, like Olivia, who have BPD.
“In the laboratory, we discovered that a particular type of stem cell can prevent BPD or regenerate newborn lungs.”
Dr. Bernard Thebaud in the neonatal intensive care unit (NICU) at The Ottawa Hospital.
“Our research uses stem cells, isolated from the umbilical cords of healthy newborns, to prevent the lung injury or even to some degree regenerate a damaged lung in the laboratory. We foresee that these stem cells, given during a certain time during the hospital stay of these babies, could prevent the progression of the lung disease.”
Unlike traditional stem cells that can directly replace damaged cells and tissues, the stem cells that Dr. Thébaud is studying work by producing healing factors that promote regeneration and repair.
Clinical trial offers hope
Dr. Thébaud and his research team have launched a phase I clinical trial to test the feasibility and safety of the stem cell treatment in premature babies. The team is doing everything in their power to make this clinical trial a success, including consulting with healthcare providers and parents of premature babies.
One thing they’ve learned from these consultations is that many parents don’t feel like they know enough about stem cells and clinical trials to decide if they want to enroll their child in the trial. So, Dr. Thébaud and his team created an animated video to explain these concepts and help parents make an informed decision. Parents can share the video with family members if they’d like a second opinion.
Jamie was involved in these consultations and her firsthand experience provided valuable insight to the research team as they planned this project. This is just one example of how researchers at The Ottawa Hospital are partnering with patients and caregivers to improve the quality and success of their research.
Dr. Bernard Thébaud looks at a premature baby in an isolette.
Dr. Thébaud and his team held a “dress rehearsal” for the clinical trial. “The dress rehearsal lets us test and tweak our tools for approaching parents, including the video, so we know what works best once we’re ready to begin offering the experimental treatment.”
If this initial trial is successful, Dr. Thébaud and his team will launch a larger Canadian clinical trial. “This is a critical step towards providing a potential breakthrough therapy that could help premature babies in Canada and around the world,” says Dr. Thébaud.
“Stem cell research is incredibly innovative. Here, we have a very promising, emerging therapy that could prevent lung injury but also improve brain development and eyesight,” says Janet Brintnell, Clinical Manager of the NICU who has seen dozens of premature babies with BPD.
“It’s amazing when you think of what it may be able to do for the quality of life for the child, for their family, and for our healthcare system. It could reduce length of stay, hospital admissions, and improve long-term outcomes. It could help these little ones lead healthier lives.”
— Janet Brintnell
“We are the only ones doing this kind of stem cell research in Canada, and there are only a few other teams in the world that are doing this.”
— Dr. Bernard Thébaud
Yet, three years ago when Olivia was in the NICU, this treatment wasn’t yet available. Now, Jamie and Tim are self-described “cheerleaders” of Dr. Thébaud’s research and are hopeful for what it might mean for future preemies and their families.
“I believe this is our future,” says Jamie. “When I think about what this could have done for our family, I wonder if Liam could have possibly survived. Olivia may not be facing the delays she’s experiencing today. Even to this day, if we are asked to put Olivia in the trial as an older candidate, we will.”
Jamie also adds the there was an impact from a mental health and financial perspective. “Our oldest child, Jacob, has had a very unusual first four years of his life because of how adaptable he has had to be during these difficult times. As a family, this entire experience has been very challenging financially due to a variety of therapies for Olivia and having to get used to becoming a single income family for several years in order to manage Olivia’s complicated schedule. All of this could have potentially been avoided if Dr. Thébaud’s research were available to our twins.”
A new beginning
Olivia is now a happy, active toddler who loves copying what her older brother Jacob does. Although, she still has BPD, it is increasingly manageable, and she no longer requires supplemental oxygen. While Olivia may suffer respiratory illness her entire life, one day a stem cell treatment developed here in Ottawa could mean that the next generation of babies with BPD won’t.
Jamie Eberts with her daughter, Olivia.
Listen to Pulse Podcast and learn how one day stem cells could heal the lungs of premature babies with Dr. Bernard Thébaud and what it could mean for parents like Jamie Eberts.
The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.
Categories: Creating Tomorrow, NICU, Stem Cell
Could cancer biotherapeutics be the next revolution in cancer treatment?
From helping the body’s own immune system better detect and fight cancer, to treating cancer with genetically-enhanced immune cells, viruses and vaccines, The Ottawa Hospital is conducting cutting-edge research that could transform cancer care right here at home and around the world.
For decades, scientists have tried to stimulate the immune system to attack cancer cells. A breakthrough came through the discovery that cancer cells make key molecules that suppress immune cells and prevent them from attacking the cancer. This discovery opened the door to revolutionary immunotherapy drugs called checkpoint inhibitors, which have shown striking results in recent years.
While promising research on checkpoint inhibitors continues, the race is now on to bring an innovative new kind of immunotherapy to patients – one that uses living cells, viruses and genes to fight cancer.
The Ottawa Hospital is a world leader in developing these innovative therapies, called cancer biotherapeutics.
“Our immune system is constantly trying to recognize and kill cancer cells, but the cancer cells are always trying to hide from it.”
— Dr. John Bell
Helping the body recognize and destroy cancer
CAR T-cell therapy is an emerging biotherapeutic treatment that harnesses the power of a patient’s own immune cells, known as T-cells, to treat their cancer. T-cells play a critical role in the immune system by killing abnormal cells, such as cells infected by germs or cancer cells. In some cancers, like acute lymphoblastic leukemia (ALL), cancerous cells become invisible to the T-cells that are meant to kill them. In CAR-T therapy the T-cells are collected and reprogrammed in the lab to recognize and destroy the cancerous cells.
“This type of immunotherapy research is groundbreaking,” said Dr. Natasha Kekre, a hematologist and associate scientist at The Ottawa Hospital, “but it is important to remember that CAR-T therapy is still very new and there can be serious side effects. We need more research to learn about this therapy and make it work for even more people and more kinds of cancer.”
The Ottawa Hospital is one of the first hospitals in Canada to participate in internationally-led CAR-T trials, and as one of Canada’s top research and treatment centres, the hospital is ideally positioned to play a lead role in bringing an innovative CAR-T research program to Canada, and to Canadian patients.
“Our goal is to build Canadian expertise and capacity for innovation in the promising CAR-T field through both laboratory research and clinical trials,” said Dr. Kekre, who is working with a team across the country. “This could lead to better CAR-T therapies that work for more kinds of cancer, as well as innovative approaches for providing CAR-T therapy in the Canadian system.”
Infecting cancer cells with viruses
Another promising biotherapeutic treatment uses oncolytic viruses that selectively infect and kill cancer cells. “Our immune system is constantly trying to recognize and kill cancer cells, but the cancer cells are always trying to hide from it,” explained Dr. John Bell, senior scientist at The Ottawa Hospital. “When you infect a cancer cell with a virus, it raises a big red flag, which helps the immune system recognize and attack the cancer.”
Recent laboratory research from Dr. Bell’s team suggests that a combination of two immunotherapies, oncolytic viruses and checkpoint inhibitors, could be much more successful in treating breast cancer and possibly other cancers.
“We found that when you add a checkpoint inhibitor after the virus, this releases all the alarms and the immune system sends in the full army against the cancer,” said Dr. Bell.
Though these methods have shown promising results, more research and clinical trials are needed.
Cancer-fighting vaccine
In addition to these techniques The Ottawa Hospital’s Dr. Rebecca Auer has found that a cell vaccine, developed in the lab using an individual’s cancer cells combined with a cancer-fighting virus, could be effective in battling cancer. Once injected, this vaccine uses a triple-threat to attack the cancer.
Dr. Rebecca Auer, The Ottawa Hospital
First, the virus only infects and kills cancer cells, leaving healthy cells unscathed. Second, the virus produces a protein called interleukin-12, which boosts the immune system’s natural ability to fight the tumour. Third, as a result, the vaccine trains the immune system to recognize and fight off the same kind of tumour if it ever comes back.
Dr. Auer and her colleagues are developing the processes required to manufacture this personalized cell vaccine and plan to initiate a “first in human” clinical trial in 2020.
Lifesaving therapies: from idea to bedside
Today, cancer care is changing at an unprecedented pace. Many patients who, only a few years ago, had few to no treatment options are now being offered hope with treatments that are more targeted and personalized. We are seeing approvals for new cancer drugs grow at an almost exponential rate, while world-class research and clinical trials are being integrated into cutting-edge cancer care.
Over the next 15 years, Canadians will see a 40 percent increase in cancer diagnoses with almost one in two developing cancer in their lifetime. Our ability to translate research into patient therapies coupled with one of the best-equipped cancer centres in the country means we are well-positioned to face this challenge head-on.
Go inside the Biotherapeutics Manufacturing Centre at The Ottawa Hospital.
The Ottawa Hospital is a leading academic health, research, and learning hospital proudly affiliated with the University of Ottawa.
Published: February 2019 For an update on Stefany’s story, click here to see what Stefany is doing now.
A game-changing cancer treatment
Stefany Dupont’s leukemia symptoms have disappeared. Her cancer was put into complete remission by a revolutionary new treatment called CAR T-cell therapy. This emerging form of immunotherapy has the potential to transform how cancer patients are treated in Canada and around the world.
Daunting odds
Stefany was first diagnosed with acute lymphoblastic leukemia (ALL) when she was just 13 years old. Children with leukemia are given a strict chemotherapy protocol that effectively cures more than 90 percent of patients. Unfortunately, this was not the case with Stefany.
She was in remission for five years but, in 2010, her leukemia came back. By then she was 18, an adult, and began receiving treatment at The Ottawa Hospital. In 2015, she received chemotherapy followed by a hematopoietic bone marrow stem cell transplant. She was on the mend until a year and a half later when she had another relapse. Adults with leukemia who relapse after a transplant have less than a 10 percent chance of survival.
“Stefany was unlucky enough to relapse within two years of her transplant,” said Dr. Jill Fulcher, Stefany’s doctor, who specializes in malignant hematology and is a clinician-investigator at The Ottawa Hospital. “But her leukemia came back with a blast and she was very sick. Palliative management was all we had to offer patients with ALL who relapsed so soon post-transplant.”
Hematologist Dr. Jill Fulcher confirms that Stefany Dupont is in remission over one year after her CAR T-cell therapy. Previously, Stefany was given a 10 to 20 percent chance of survival, pre-CAR T-cell treatment.
New hope
Dr. Fulcher and her colleague Dr. Natasha Kekre, a hematologist and associate scientist at The Ottawa Hospital, knew that clinical trials in the United States, using CAR T-cell immunotherapy, showed promising results in children and adolescents with leukemia and blood cancers, putting many into long-lasting remission.
For patients like Stefany who are extremely sick and out of options, CAR T-cell therapy offers new hope. That’s why Dr. Kekre is leading the charge to bring CAR T-cell immunotherapy to The Ottawa Hospital.
Giving Canadians access to leading-edge treatments
As one of Canada’s leading research and treatment centres, equipped with world-leading expertise, The Ottawa Hospital is ideally positioned to help bring this innovative treatment to Canada, and to Canadian patients. The Ottawa Hospital is one of the first hospitals in Canada to participate in internationally-led CAR-T trials, and the Hospital is now playing a lead role in a made-in-Canada CAR-T research program.
“Our goal is to build Canadian expertise and capacity for innovation in the promising CAR-T field through both laboratory research and clinical trials,” said Dr. Kekre, who is working with a team across the country. “This could lead to better CAR-T therapies that work for more kinds of cancer, as well as innovative approaches for providing CAR-T therapy in the Canadian system.”
From translational research to trial design to manufacturing, The Ottawa Hospital, alongside BC Cancer, is ideally positioned to shepherd this complex trial of an experimental therapy to our patients.
“It’s well recognized that Ottawa is a world leader in clinical trials and innovative trial designs,” said Dr. Manoj Lalu, associate scientist and anesthesiologist at The Ottawa Hospital who is part of the CAR-T team. “Many of the guidelines produced internationally around trial design and reporting originate from The Ottawa Hospital.”
Dr. Natasha Kekre is working with other hospitals across Canada to develop a “made-in-Canada” approach for CAR-T cancer therapy.
About CAR-T Therapy
CAR T-cell therapy harnesses the power of a patient’s own immune cells, known as T-cells, to treat their cancer. T-cells play a critical role in the immune system by killing abnormal cells, such as cells infected by germs or cancer cells. In some cancers, like acute lymphoblastic leukemia (ALL), cancerous cells become invisible to the T-cells that are meant to kill them. In CAR-T therapy the T-cells are collected and reprogrammed in the lab to recognize and destroy the cancerous cells.
“This type of immunotherapy research is groundbreaking,” said Dr. Kekre, “but it is important to remember that CAR-T therapy is still very new and there can be serious side effects. We need more research to learn about this therapy and make it work for even more people.”
A well-deserved reprieve
CAR-T treatment was not yet available in Canada when Stefany needed it. So, her only option at the time was to try to join a CAR-T clinical trial at the Children’s Hospital of Philadelphia. Since the hospital’s clinical trial was still accepting patients with ALL up to 25 years of age, Stefany was eligible to participate.
Three months following Stefany’s CAR T-cell infusion in Philadelphia, she had a bone marrow biopsy that showed she was in remission — her treatment was working.
Three months after that, Stefany went on a well-deserved trip.
“After the sixth month waiting time, I went to Australia,” said Stefany. She visited Sydney, Brisbane, Melbourne, went scuba diving at the Great Barrier Reef, and hang-gliding over the shores of Byron Bay. It was a wonderful break after the intensive treatment.
“It is a really good sign that Stefany has remained in remission for over 2 years after having CAR T-cell therapy,” said Dr. Fulcher. “Without this therapy, she definitely would not be with us today.”
Unique biotherapeutics facility
CAR-T therapy needs to be individually manufactured for each patient, using a patient’s own cells combined with large amounts of highly pure virus to deliver the CAR gene. The Ottawa Hospital’s Biotherapeutics Manufacturing Centre is ideally positioned to manufacture this kind of therapy because it has the most advanced system to make the clinical grade virus needed to create CAR T-cells for clinical trials. This is the only facility in Canada that has produced this kind of virus for clinical trials.
“With our unique manufacturing facility, our expertise in clinical trials and our world-class cancer and hematology programs, The Ottawa Hospital is ideally positioned to lead the way in developing the next generation of CAR-T therapy,” said Dr. Rebecca Auer, Director of Cancer Research at The Ottawa Hospital.
“The Ottawa Hospital is ideally positioned to lead the way in developing the next generation of CAR-T therapy.” – Dr. Rebecca Auer
“Patients with ALL, lymphoma, and other blood cancers could benefit from this experimental treatment,” said Dr. Kekre. The hope is that one day CAR T-cell therapy may also be a treatment for a variety of cancers, such as breast and colorectal cancer. It is through clinical trials conducted at The Ottawa Hospital that innovative cancer treatments will be discovered and will continue to offer hope to patients like Stephany.
Organizations such as BioCanRx, the Canada Foundation for Innovation, and the Government of Ontario have supported The Ottawa Hospital’s CAR-T research and the Biotherapeutics Manufacturing Centre, but additional funding is essential to make this program a reality.
January 2023 update:
It’s been a rollercoaster of a ride for Stefany in the last year. Since December 2021, she’s struggled with lung infections, which she developed as a result of being immunocompromised and because, since 2017, she has important scarring on her lung. Such scars are the result of what happened to her while she was on a months-long waiting list to get to the CAR-T program in Philadelphia. “My [leukemic] condition got worse, I contracted pneumonia with no functional immune system, and despite overcoming it, I was left with considerable scarring on my lung, putting it at risk for various infections.”
It’s for this reason, Stefany is grateful to hear patients in a Canadian-first clinical trial at our hospital are getting access to CAR T-cell therapy right here in Ottawa. “Thankfully, the participants don’t have to go through what I’ve gone through with pneumonia and the waiting,” says Stefany.
She is slowly improving and is hoping to become a schoolteacher in the future. Stefany’s currently tutoring students and has given presentations on social justice topics to secondary school students. She’s also been enjoying some travel recently, including a nature expedition that supports youth affected by cancer and is looking forward to trips to Mexico and Costa Rica in 2023.
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