Targeting Macrophages with CAR T Cells Delays Solid Tumor Progression and Enhances Antitumor Immunity.

ABSTRACT: Tumor-associated macrophages (TAM) are one of the most abundant cell types in many solid tumors and typically exert protumor effects. This has led to an interest in macrophage-depleting agents for cancer therapy, but approaches developed to date have had limited success in clinical trials. Here, we report the development of a strategy for TAM depletion in mouse solid tumor models using chimeric antigen receptor (CAR) T cells targeting the macrophage marker F4/80 (F4.CAR-T). F4.CAR-T cells effectively killed macrophages in vitro and in vivo without toxicity. When injected into mice bearing orthotopic lung tumors, F4.CAR-T cells infiltrated tumor lesions and delayed tumor growth comparably with PD-1 blockade, and significantly extended mouse survival. Antitumor effects were mediated by F4.CA

SUBMITTER: Sanchez-Paulete AR 

PROVIDER: S-EPMC10704925 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature