Activation of Cell-Intrinsic Signaling in CAR-T Cells via a Chimeric IL7R Domain.

ABSTRACT: Chimeric antigen receptor (CAR) T cells can effectively treat leukemias, but sustained antitumor responses can be hindered by a lack of CAR T-cell persistence. Cytotoxic effector T cells are short-lived, and establishment of CAR-T cells with memory to ensure immune surveillance is important. Memory T cells depend on cytokine support, with IL7 activation of the IL7 receptor (IL7R) being critical. However, IL7R surface expression is negatively regulated by exposure to IL7. We aimed to support CAR T-cell persistence by equipping CAR-T cells with a sustained IL7Rα signal. We engineered T cells to constitutively secrete IL7 or to express an anti-acute myeloid leukemia-targeted IL7Rα-chimeric cytokine receptor (CCR) and characterized the phenotype of these cell types. Canonical downstream signal

SUBMITTER: Vorri SC 

PROVIDER: S-EPMC11382189 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature