Successful targeting of PD-1/PD-L1 with chimeric antigen receptor-natural killer cells and nivolumab in a humanized mouse cancer model.

ABSTRACT: In recent decades, chimeric antigen receptor (CAR)-engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their efficacy remains unsatisfactory on solid cancers, plausibly due to the influence of tumor microenvironments (TME). In a novel mouse cancer model with a humanized immune system, tumor-infiltrating immunosuppressive leukocytes and exhausted programmed death protein-1 (PD-1)^high T cells were found, which better mimic patient TME, allowing the screening and assessment of immune therapeutics. Particularly, membrane-bound programmed death ligand 1 (PD-L1) level was elevated on a tumor cell surface, which serves as an attractive target for natural killer (NK) cell-mediated therapy. Hematopoietic stem cell-derived CAR-NK (CAR pNK) cel

SUBMITTER: Liu WN 

PROVIDER: S-EPMC9683725 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature