CAR T
Published on February 13, 2025
CAR-Ms that suppress furin studied for use against solid tumors
by Nature
Ziane-Chaouche L, Raffo-Romero A, Hajjaji N, et al. Inhibition of Furin in CAR Macrophages Directs Them Toward a Proinflammatory Phenotype and Enhances Their Antitumor Activities. Cell Death & Disease. 2024; (doi: 10.1038/s41419-024-07267-4).
Researchers suggest that engineering second-generation chimeric antigen receptor macrophages (CAR-Ms) that suppress furin could move science closer to effective therapeutic solutions for solid tumors. Macrophages are under exploration as an alternative in CAR T-cell therapy to T lymphocytes, whose antitumor potential is limited in the setting of solid tumors by challenges infiltrating those dense and complex microenvironments. Furin is a logical target because it is overexpressed in the presence of tumor cells. Evidence indicates that CAR-Ms that inhibit furin had certain advantages over CAR-Ms that express the proprotein convertase. Specifically, they demonstrated greater antitumor phagocytic activity against breast cancer cells and ex vivo patient-derived tumoroids. They also kept a persistent proinflammatory profile — a potential signal of robust tumoricidal potential. Furin-suppressed CAR-Ms also secreted factors that stimulate T-cell activation. Collectively, these properties could address inadequate T-cell infiltration and sensitivity to local immunosuppression, two important barriers in the application of CAR T-cell therapy to solid tumors.
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