Canadian cancer survivor works with the NRC for broader access to CAR-T therapy

- Ottawa, Ontario

After undergoing years of chemotherapy and stem-cell transplants for large B-cell lymphoma, Owen Snider was told that he wouldn't live to see another Christmas. But a new cancer treatment called chimeric antigen receptor (CAR) T-cell therapy gave him an enduring chance at life—and instilled in him a passion for telling the world about this amazing innovation.

He's now helping researchers from the National Research Council of Canada (NRC) better understand the patient's perspective as they work to advance CAR T-cell therapies in Canada and make them more accessible to Canadians.

Creating CAR T-cells involves growing human T cells in a laboratory and modifying them using a viral vector so they can recognize and attack cancer.

CAR-T therapy uses a patient's own T-cells, a type of immune cell that can kill abnormal cells like cancer cells or those infected by germs. Scientists collect T-cells from a patient, genetically reprogram them in a lab to hunt and destroy cancerous cells and reinfuse them into the person.

"Working with CAR T-cells, our researchers are developing treatments for patients who have lost hope that anything will work for them," says Sue Twine, Director General of the NRC's Human Health Therapeutics Research Centre. "When you can offer those patients a fighting chance using their own blood cells as a weapon, you can't help but feel passionate about your work."

The NRC's contribution to developing this new made-in-Canada treatment builds on decades of global leadership in crafting breakthrough therapies. Lessons learned from this CAR T-cell therapy will be valuable for research on other diseases such as brain, pancreatic and lung cancers.

A retrospective: Canada's first CAR-T clinical trial

The first Canadian-made CAR-T clinical trial was a cross-Canada partnership by the Canadian-led Immunotherapies in Cancer (CLIC) program, founded by researchers at The Ottawa Hospital, BC Cancer and BioCanRx. For this first Canadian manufactured CAR-T trial, referred to as the CLIC-01, the CAR T-cells were manufactured in Victoria, British Columbia, and the clinical treatment was held in Ottawa, Ontario, with other clinical sites added later. This study paved the way for even more innovative CAR-T therapies, some of which will be tested in an upcoming NRC developed CLIC-02 CAR-T clinical trial that's expected to open in early 2024 in Vancouver, Ottawa and Toronto.

To qualify for the CLIC-01 trial in 2020, Owen underwent 6 weeks of tests and scans. Aged 73 at the time, he feared he might be too old. But he was in good physical shape despite a heart condition and other issues, so he got the "stamp of approval" to proceed. In June 2020, he checked into the Ottawa Hospital Transplantation and Cellular Therapy Program. The team removed some of his white blood cells and sent them to a lab in Victoria, where the T-cells were extracted, re-engineered with the CAR protein and grown to large numbers. The whole process only took a couple of weeks, after which Owen received a low dose of chemotherapy to prepare his body for the CAR-T treatment and then the modified CD19 CAR T-cells were put back into Owen's bloodstream at the Ottawa clinical trial site.

"At my checkup, 30 days after getting my T-cells back, the scan showed that I was almost clear of cancer," he says. By the 3-month mark, he was "clean as a whistle." Almost 3 years later, with the modified T-cells still in Owen's bloodstream continuing to scan for and destroy any returning cancer cells, there is still no sign of lymphoma.

NRC scientists reprogramming T-cells to create CAR T-cells

In the first clinical trial, researchers aimed to demonstrate to Health Canada that the CAR-T therapy manufactured at one site could be transported across Canada and used safely in patients elsewhere. So far, the trial's findings, reported in a 2022 research article in Frontiers in Immunology, not only show that the CAR-T treatments can be safely manufactured and transported but that the cells also maintain similar activity to the more expensive commercial CAR-T therapy. On the heels of this initial success, the team of researchers and doctors are working with the NRC to expand manufacturing and training of highly qualified personnel to other sites across the country. This would reduce wait times and costs and improve access to these revolutionary CAR-T therapies for Canadians regardless of where they live.

The NRC's Disruptive Technology Solutions for Cell and Gene Therapy Challenge program has now provided funding to the 2 key Canadian research networks to help expand cell therapy manufacturing capacity. The Canadian Cell Manufacturing Network is working to add workspace for modifying patient T-cells with CAR genes, while Centre of Excellence for the Commercialization of Cellular Immunotherapy (known as C3i) will be expanding capacity for lentiviral vectors—a critical component in CAR-T therapies.

A look forward: widening the CAR-T road with the NRC

The clinical trial for a new NRC-developed CAR-T therapy will take CAR-T treatments to new heights.

The NRC has been working with researchers and clinical partners across Canada for several years to develop a novel antibody that targets another protein in patients with leukemia and lymphoma cancers, CD22. This therapy is different from the one targeting CD19 in the first trial, so patients who did not respond well in the CLIC-01 trial may get another chance. The new CD22 CAR-T therapy will also be tested on both children and adults.

"This is a completely new, made-in-Canada discovery that the world will be watching," says Sue Twine.

Looking ahead, Scott McComb, a research officer with the NRC cancer immunology team and adjunct professor at the University of Ottawa, can see numerous possibilities for applying CAR-T therapies. "We're aiming to create a toolbox with new CARs targeting many cancer proteins," he says. "This will give patients more options and provide healthcare specialists with more resources to work with." It may also lead to treatments for a variety of hard-to-treat cancers, such as pancreatic cancer.

That's music to the ears of patients like Owen, who points out that T-cell therapy is easier on the body and spirit, and much faster than the chemo or "gruelling" stem-cell transplants. He hopes that once the treatment has been approved by Health Canada, it can become the go-to solution for lymphomas like his and that he can help researchers create CAR-T successes for patients with many other types of cancer as well.

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