Reprogramming glutamine metabolism enhances BCMA-CAR T-cell fitness and therapeutic efficacy in multiple myeloma.

ABSTRACT:

Abstract

Glutamine dependence of cancer cells reduces local glutamine availability, which hinders antitumor T-cell functionality and facilitates immune evasion. We thus speculated that glutamine deprivation might be limiting efficacy of chimeric antigen receptor (CAR) T-cell therapies in patients with cancer. We have seen that antigen-specific T cells are unable to proliferate or produce interferon gamma (IFN-γ) in response to antigen stimulation when glutamine concentration is limited. Using multiple myeloma (MM) as a glutamine-dependent disease model, we found that murine CAR T cells selectively targeting B-cell maturation antigen (Bcma) in MM cells were sensitive to glutamine deprivation. However, CAR T cells engineered to increase glutamine uptake by expression of the glutamine

SUBMITTER: Navarro F 

PROVIDER: S-EPMC12824695 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature