Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells.

ABSTRACT: The integration of molecular targeted therapeutics with chimeric antigen receptor T (CAR-T) cell therapy represents a novel strategy to amplify the anti-tumor efficacy of immunotherapy. While CD19-targeted CAR-T cells and Janus kinase (JAK) inhibitors have independently shown efficacy against certain B-cell leukemias, such as Philadelphia chromosome-like acute lymphoblastic leukemia, the concurrent use of JAK1/2 inhibitors, such as ruxolitinib, has been implicated in reducing CAR-T cell potency by inhibiting the JAK1-dependent T cell activation pathway. This study explores the combinatorial use of a selective type II JAK2 inhibitor, CHZ868, with CD19 CAR-T cells, revealing a synergistic enhancement of anti-leukemic activity across B-cell tumor models irrespective of JAK2 mutational status.

SUBMITTER: Mitsuno K 

PROVIDER: S-EPMC11787079 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature