Impact on Patients
Recent success
Significant investment by our philanthropic partners enabled the creation at the University of Calgary in 2020 of a research program in cell and immune therapy called ACTION, or the Alberta Cellular Therapy and Immune Oncology Initiative. This program has brought together scientists and clinicians possessing diverse and complementary skills and expertise and has enabled them to invent novel cell and immune therapies and engineer solutions to problems facing the existing arsenal of CAR T treatments.
Building on the foundation and momentum of the ACTION initiative, cancer immunotherapy research at the University of Calgary has transitioned to the Riddell Centre for Cancer Immunotherapy. Riddell Centre investigators are currently developing more than a dozen novel cell and immune therapies for cancer, several of which have entered, or are close to entering clinical trial.
The most advanced of these is a novel CAR T-cell therapy called GCAR1, invented by ACTION scientists in 2021 to attack a rare soft tissue sarcoma called alveolar soft part sarcoma (ASPS). The treatment was designed to treat a former patient of the Alberta Children’s Hospital but was first tested in a relapsed / refractory ASPS patient from rural Quebec who travelled to Calgary for treatment in late 2023. To our knowledge, that clinical trial represents the first time that a novel CAR T cell therapy was invented, developed and manufactured by Canadian scientists and delivered to a patient in Canada. Two additional CAR T therapies invented and developed by our investigators for lymphoma and myeloma, respectively, are also moving rapidly toward clinical translation, with phase I studies anticipated to open in mid- to late-2025.
Dr. Franz Zemp, Adjunct Assistant Professor and Inventor of GCAR1
Current and future impact
GCAR 1 - a second generation CAR T cell therapy for alveolar soft part sarcoma (ASPS) and other GPNMB-expressing cancers.
In 2021, Drs. Franz Zemp and team within the Mahoney Lab developed GCAR1, an engineered CAR T-cell therapy targeting a protein called GPNMB found on ASPS cells. GCAR1 was found to be safe and effective at killing cancer cells in preclinical models of the patient’s disease. With support from local and national biomanufacturing partners, GCAR1 was made to clinical trial standards and received Health Canada approval for a clinical trial.
The newly developed CAR T-cell therapy was well received by the research and clinical community and has opened the door to a single patient study. Led by Dr. Mona Shafey and colleagues, GCAR1 has been used as an experimental treatment for a woman with ASPS. The patient received the treatment at the Tom Baker Cancer Centre in late 2023. They tolerated the treatment well and results from this study will be published soon.
The discovery of GPNMB's presence in other solid tumors, including rare sarcomas and forms of kidney and breast cancer, prompted the development of a Phase I basket trial for GCAR1 with funding from the Canadian Institutes of Health Research. Riddell Centre researchers are collaborating with the Canadian Cancer Trials Group to launch this study in mid-2025, offering this innovative treatment nationwide.
BCAR1, a second generation BCL2L1-armoured BCMA-CAR T therapy for multiple myeloma.
Multiple myeloma, a blood and bone marrow cancer of antibody producing immune cells known as plasma cells, is the second most common hematological malignancy.
In recent years, new treatments have emerged for patients with relapsed or refractory multiple myeloma, including CAR T cell therapy targeting the B-cell maturation antigen (BCMA) – a protein universally expressed on multiple myeloma cells. In 2020, Dr. Nizar Jacques Bahlis and Dr. Paola Neri at the Arnie Charbonneau Cancer Institute in Calgary interrogated myeloma and immune cells (including CAR T cells) genome in patients treated with BCMA-targeting CAR T cells in an effort to define why this medicine was failing in some patients. Through this work, they identified a number of genes, including the BCL2L1 gene, that are highly expressed in the CAR T cells collected from patients with a deeper and more durable overall response.
Harnessing that important observation, the Bahlis and Neri teams armored BMCA-targeting CAR T cells with the BCL2L1 gene, and found that this enhances their viability and activity, and overcame challenges like immune cell exhaustion. Pre-clinical studies have also shown very promising results. The team is now working with biomanufacturing partners in Vancouver and Ottawa to manufacture BCAR1 (a BCL2L1-armored CAR) to GMP, and prepare for a Phase 1 clinical trial in 2025. This novel CAR T design may also be beneficial for other cancers like glioblastoma and sarcoma.
CD22 Advancing Blood Cancer Treatments: From Development to Clinical Trials
CAR T cell therapies have revolutionized the treatment of certain blood cancers, like B-cell leukemias and lymphomas, by modifying a patient's own T cells to express CARs that target specific proteins on cancer cells. These therapies have shown remarkable response rates and durable remissions in some patients. However, the personalized nature of CAR T therapy, which involves genetically engineering each patient's own cells, requires significant infrastructure and expertise for safe and successful manufacturing and delivery.
One of our clinician scientists, Dr. Kevin Hay, focuses on developing novel CAR T cell therapies for blood cancers. Alongside Dr. Natasha Kekre from the Ottawa Hospital, his team at BC Cancer co-led a clinical trial assessing the safety and efficacy of the ‘Made-in-Canada’ CLIC-1901 CAR T therapy in patients with relapsed/refractory CD19 positive acute lymphoblastic leukemia and non-Hodgkin’s lymphoma, marking the first trial of in-house manufactured CAR-T cells in Canada. This trial demonstrated that administering fresh CLIC-1901 product is fast, safe, and efficacious, providing valuable insights for creating feasible and sustainable CAR-T cell programs in resource-constrained settings.
Dr. Hay will continue this research in Calgary, with funding from Canadian Institutes of Health Research grants. In collaboration with the National Research Council and the CLIC program, he will lead a phase 1 trial targeting CD22, another protein linked to B-cell cancers. The trial, sponsored by the British Columbia Cancer Agency and called CLIC-2201, will test, manufacture, and distribute CD22 CAR T-cells and commence in 2024 at multiple sites across Canada (including a pediatric and adult site in Calgary), offering hope to young children, adolescents and adults with relapsed B cell malignancies.
This work is possible thanks to our many collaborators
