Project 466359

Chimeric antigen receptor (CAR)-T cells targeting CD19, a marker on B cell cancers, have led to meaningful and durable remissions for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), and is now a standard therapy in Canada for children and young adults. This therapy is manufactured by isolating cells of the immune system called T cells from a patient, inserting the 'CAR' into the T cells so that it can recognize cancer cells, growing the cells in a clinical laboratory, and then infusing the CAR-T cells back into the patient. Despite the success of CD19 CAR-T cells, unfortunately only 30-50% of patients with B-ALL have a durable remission or cure after receiving therapy. One of the reasons for this is that the cancer 'escapes' CD19 targeting, losing this marker on the surface of the cancer cells. Using our research team's expertise in this therapy, we have designed CAR-T cells that targets a different marker, CD22, for the treatment of patients with B cell cancers, including those who have relapsed after CD19 CAR-T cells. The product we have designed to target CD22 uses a binder derived from llamas called a single domain antibody, which has potential advantages over standard mouse or human antibody-based CARs, so that the cells may be more robust and not become exhausted over time in the body, leading to better clinical outcomes. Our proposal is to take this CD22 CAR-T cell product into an early phase clinical trial for pediatric and adult patients. The main objective of this trial is to determine a safe dose to use in a subsequent trial that will be designed to make this an approved standard therapy for patients. In this project, we will also look at tumour and blood samples to assess for markers that could predict how well the product works and to determine ways to improve this and other CAR-T cell products in the future.