The National Research Council of Canada (NRC) has developed a groundbreaking CAR T-cell therapy targeting the CD22 protein on cancer cells, offering new hope for patients with B-cell leukemia and lymphoma who have not responded to existing treatments.
NRC researcher Mehdi Arbabi-Ghahroudi discovered and characterized a unique anti-CD22 antibody that forms the foundation of this innovative therapy. "This unique type of engineered single domain antibody, also called a nanobody, has superior properties over conventional antibody fragments," explains Arbabi-Ghahroudi. "With it, the NRC's research team was able to create a new made-in-Canada CAR T-cell that can detect the CD22 protein on B-cell leukemia and lymphoma cells."
The therapy's ability to target CD22 provides a crucial alternative for patients who have relapsed after treatments targeting other cancer proteins such as CD19. This represents a significant advancement in the field of immunotherapy for blood cancers.
Clinical Trials Set to Begin
The NRC's CD22 CAR T-cell therapy is scheduled to enter clinical trials in late 2023 across three Canadian cities: Vancouver, Ottawa, and Toronto. Two parallel trials will be conducted – one focusing on pediatric and adult lymphoblastic leukemia and the other on lymphoma.
These trials will be integrated into the Canadian-Led Immunotherapies in Cancer (CLIC) program, founded by researchers at The Ottawa Hospital, BC Cancer, and BioCanRx, highlighting the collaborative nature of this Canadian innovation.
Addressing Accessibility Challenges
While six different CAR T-cell therapies have received FDA approval for blood cancers, with five also approved by Health Canada, these treatments remain largely inaccessible to Canadian patients due to prohibitive costs and limited provincial healthcare coverage. Additionally, all currently approved therapies are manufactured outside Canada, resulting in extended wait times – a luxury many cancer patients cannot afford.
"Our research focuses on developing more affordable and accessible CAR T-cell therapies," says NRC researcher Scott McComb, project lead for CAR-T development for blood cancers. "There's no point in making fancy new therapies if Canadians can't access them."
Building a Canadian Biomanufacturing Ecosystem
A key innovation in the NRC's approach is the establishment of a network of biomanufacturing facilities across Canada capable of producing clinical CAR-T products under good manufacturing practices. This distributed manufacturing model would allow hospitals and clinics to extract and modify patient T-cells on-site, creating personalized therapies with potentially lower costs and faster delivery times.
Risini Weeratna, who leads the NRC's Cell and Gene Therapy Challenge program, emphasizes the broader impact: "The CGT program has had a revolutionary impact on our ability to deliver these therapies in Canada. We're not only innovating, but also helping to establish a whole ecosystem around cell and gene therapy."
Building on a Legacy of Innovation
The NRC has a distinguished history in biotherapeutics, including the development of the first meningitis vaccine in the early 1980s and the world's first synthetic human proinsulin gene, which forms the basis for insulin medications used globally today.
"We fused the collective NRC knowledge of fundamental biology of immune cells and our expertise in the production of antibodies to create this new made-in-Canada CAR T-cell therapy," explains McComb. "What we learn from our research into leukemia and lymphoma will also help us build breakthrough therapies for other diseases such as brain, pancreatic and lung cancer."
Alternative Approaches to CAR T-Cell Therapy
While the NRC advances its patient-derived (autologous) CAR T-cell therapy, other research institutions are exploring complementary approaches. The National University Cancer Institute, Singapore (NCIS) is trialing an allogeneic CAR T-cell therapy that uses T-cells from healthy donors rather than patients themselves.
This approach addresses a key limitation of traditional CAR T-cell therapies. As Dr. Tan Lip Kun, Senior Consultant at NCIS explains, "In autologous CAR T-cell therapies, the T cells are obtained from cancer patients. These patients tend to have high-risk, relapsed or resistant cancers, and would have undergone several courses of chemotherapy or other types of immunotherapy, so their own T cells are fewer and weaker."
Future Implications
The NRC's work represents a significant step forward in Canada's capacity to develop and deliver cutting-edge cancer treatments domestically. If successful in clinical trials, this made-in-Canada therapy could transform the treatment landscape for blood cancers while establishing a model for more accessible cell therapies.
As Weeratna summarizes: "With our collaborative network of clinical and industry partners, we can continue the tradition of putting all the critical elements together to effect real change in how we treat cancer in Canada."
