靶向成纤维细胞活化蛋白的嵌合抗原受体巨噬细胞

Under the rapid advancement of chimeric antigen receptor T cell (CAR-T) technology, CAR-macrophages (CAR-Ms) are also being developed currently in the pre-clinical stage and have been shown to inhibit tumor growth in several mouse tumor models. Fibroblast activation protein (FAP) is a type II transmembrane serine protease, which is expressed in stromal fibroblasts of over 90 % of common human epithelial cancers and is upregulated in fibrotic diseases of the liver, lung and colon, etc.

In this study, we firstly constructed FAP-CAR macrophages to target FAP + cells through in vitro phagocytosis assays. In subsequent in vivo assays, we discovered that FAP-CAR- ZETA bone marrow-derived macrophages (BMDMs) rather than FAP-CAR BMDMs, exhibited a pronounced anti-tumor effect in mouse subcutaneous MC38 colon cancer model.

In addition, FAP-CAR and FAP-CAR- ZETA BMDMs therapy could effectively improve CCl 4 -induced liver fibrosis in mice. Collectively, CAR-Ms targeting FAP demonstrated great therapeutic potential in cancer and liver fibrosis therapy.