GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity.

ABSTRACT: Inhibitory myeloid cells and their cytokines play critical roles in limiting chimeric antigen receptor T (CART) cell therapy by contributing to the development of toxicities and resistance following infusion. We have previously shown that neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF) prevents these toxicities and enhances CART cell functions by inhibiting myeloid cell activation. In this report, we study the direct impact of GM-CSF disruption during the production of CD19-directed CART cells on their effector functions, independent of GM-CSF modulation of myeloid cells. In this study, we show that antigen-specific activation of GM-CSF^KO CART19 cells consistently displayed reduced early activation, enhanced proliferation, and improved anti-tumor acti

SUBMITTER: Cox MJ 

PROVIDER: S-EPMC9234947 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature