BCL2L1 armored CAR T cells overcome exhaustion and enhance persistence in multiple myeloma
Funding Cycle:
2023-2024Name:
Nizar BahlisType of Award:
Translational Research AwardHome Institution:
University of CalgaryDescription
The specific aims of this proposed study aim to enhance CAR T cell therapy for multiple myeloma by addressing the mechanisms of resistance and improving persistence of CAR T cells armored with BCL-xL. Aim 1 seeks to determine the role of MM cell death ligands in the resistance of BCL-xL armored CARs to activation-induced cell death (AICD), focusing on death receptor-independent mechanisms. Aim 2 aims to define, at transcriptomic, epigenomic, and metabolic levels, the factors driving the metabolic fitness and persistence of BCL-xL armored CARs, exploring pathways beyond death receptors downstream signaling. These studies aim to provide insights into overcoming resistance and improving the efficacy of CAR T cell therapy for multiple myeloma.
