In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma.

ABSTRACT: Chimeric antigen receptor (CAR) T cells are highly effective in haematological malignancies¹. However, progressive loss of CAR T cells contributes to relapse in many patients^2-4. Here we performed in vivo loss-of-function CRISPR screens in CAR T cells targeting B cell maturation antigen to investigate genes that influence CAR T cell persistence and function in a human multiple myeloma model. We tracked the expansion and persistence of CRISPR library-edited T cells in vitro and at early and late time points in vivo to track the performance of gene-modified CAR T cells from manufacturing to survival in tumours. The screens revealed context-specific regulators of CAR T cell expansion and persistence. Ablation of RASA2 and SOCS1 enhanced T cell expansion in vitro, whereas

SUBMITTER: Knudsen NH 

PROVIDER: S-EPMC12806180 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature