Efficacy and safety evaluation of cross-reactive Fibroblast activation protein scFv-based CAR-T cells

交叉反应成纤维细胞活化蛋白scFv的CAR-T细胞疗效及安全性评估

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作者:Wenhao Niu #, Binchen Wang #, Yirui Zhang, Chaomin Wang, Jing Cao, Jiali Li, Yong He, Ping Lei

Discussion

Taken together, the human/murine cross-reactive FAP-CAR T cells were powerfully potent in killing human and murine FAP positive tumor cells and CAFs. They were biologically safe and exhibit low-level OTOT, warranting further clinical investigation into our FAP-CAR T cells.

Methods

In this study, we designed second-generation CAR T cells targeting FAP with 4-1BB as a co-stimulatory molecule, and tested their cytotoxicity against FAP-positive cells (hFAP-HT1080 cells and a variety of primary CAFs) in vitro and in Cell line-derived xenograft (CDX) and a patient-derived xenograft (PDX) model.

Results

Results showed that our FAP-CAR T cells were powerfully potent in killing human and murine FAP-positive tumor cells and CAFs in multiple types of tumors in BALB/c and C57BL/6 mice and in patient-derived xenografts (PDX) model. And they were proved to be biologically safe and exhibit low-level OTOT.

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