CAR T cells, CAR NK cells, and CAR macrophages exhibit distinct traits in glioma models but are similarly enhanced when combined with cytokines.

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Tác giả: Niklas Binder, Manon Bouzereau, Alicia Buck, Serena Fazio, Julia Frei, Thomas Look, Maximilian Mastall, Cesar Nombela Arrieta, Steve Pascolo, Francesco Prisco, Roman Sankowski, Frauke Seehusen, Berend Snijder, Miaomiao Sun, Tobias Weiss, Michael Weller, Conrad Wyss

Ngôn ngữ: eng

Ký hiệu phân loại: 621.384196 Electrical, magnetic, optical, communications, computer engineering; electronics, lighting

Thông tin xuất bản: United States : Cell reports. Medicine , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 679312

Chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy against cancer. Although there is a growing interest in other cell types, a comparison of CAR immune effector cells in challenging solid tumor contexts is lacking. Here, we compare mouse and human NKG2D-CAR-expressing T cells, natural killer (NK) cells, and macrophages against glioblastoma, the most aggressive primary brain tumor. In vitro we show that T cell cancer killing is CAR dependent, whereas intrinsic cytotoxicity overrules CAR dependence for NK cells, and CAR macrophages reduce glioma cells in co-culture assays. In orthotopic immunocompetent glioma mouse models, systemically administered CAR T cells demonstrate superior accumulation in the tumor, and each immune cell type induces distinct changes in the tumor microenvironment. An otherwise low therapeutic efficacy is significantly enhanced by co-expression of pro-inflammatory cytokines in all CAR immune effector cells, underscoring the necessity for multifaceted cell engineering strategies to overcome the immunosuppressive solid tumor microenvironment.
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