Principal Investigator:
Elie Haddad
CHU Ste-Justine
Co-investigators
Nicolas Prud’Homme, Fabien Touzot, Henrique Bittencourt
CHU Ste-Justine
Project of $2,213,403 over 3 years
- Supported by CQDM through: Ministère de l’Économie, de l’Innovation et de l’Énergie du Québec (MEIE)
- And by a co-funding partner:
- The Cole Foundation
- Immugenia
- Canadian Cancer Society
- Oncopole-pôle cancer du FRQS
Challenge
The Chimeric Antibody Receptor (CAR) presents a promising avenue in cancer immunotherapy by engineering patients’ T cells to express CAR molecules, enabling targeted recognition and elimination of tumor cells. While CAR-T therapy has demonstrated notable success in inducing remission for B cell leukemia, lymphoma, and multiple myeloma, it has failed in non-hematologic solid tumors, with relapses posing a significant challenge. A key issue lies in the exhaustion of CAR-T cells, hindering their long-term viability. Furthermore, immediate, and severe side effects following infusion have been observed. Addressing these hurdles is crucial to enhance the durability and safety of CAR-T immunotherapy, especially in the context of non-hematologic solid tumors.
Solution
The research team has designed a tool to introduce safely the CAR in hematopoietic stem cells (HSC). Since the CAR is introduced in HSC, theoretically, all the blood cells should express it, which would be dangerous. The team’s invention limits CAR expression to the two major cells of the immune system (T and NK cells) capable of killing tumor cells. This strategy would: 1) result in a continuous replenishment of CAR cells to kill tumor cells; 2) reduce risks of side effect because of their progressive appearance; and 3) allow a continuous surveillance system for relapses. The research team plans to test their strategy in pediatric pre-B acute lymphoblastic leukemia (B-ALL) and rhabdomyosarcoma (RMS).
Expected Achievements /Impacts
The research team aims to establish a proof-of-concept demonstrating the feasibility of the proposed strategy in pediatric cancers. This involves conducting preclinical assays that will enable Immugenia, a Quebec-based start-up, to advance this technology towards clinical trials. The project’s success in generating key proof-of-concept data is expected to accelerate Immugenia’s development program, attract investment, and foster the creation of high-quality jobs within Quebec’s biotechnology ecosystem. Ultimately, these achievements are expected to lay the foundation for groundbreaking clinical trials aimed at treating children with B-ALL or RMS not only in Quebec but also extending across Canada.
