Establishment of FAP-overexpressing Cells for FAP-targeted Theranostics

Jian, H.; Niu, Wenhao; Xu, Zhuoshuo; Zhu, Jianmeng; Pan, Xin; Zhang, Y.-C.; Lei, Ping; Huang, Fan; He, Yong

doi:10.1007/s11596-023-2740-7

Cited by 1 publication

(2 citation statements)

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“…In that most of the tumor cells themselves rarely expressed FAP, hFAP overexpressed cell line FAP-HT1080 was established ( 16 ) for the subsequent test ( Figure 2A ). When CARTs were co-cultivated with targets, they elicited cytotoxicity against hFAP-HT1080 and U87MG cells in a E/T ratio-dependent manner, but not against FAP-negative HT1080 cells.…”

Section: Resultsmentioning

confidence: 99%

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

Niu,

Wang,

Zhang

et al. 2024

Front. Immunol.

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IntroductionFibroblast activation protein (FAP) overexpression on cancer-associated fibroblasts (CAFs) is associated with poor prognosis and worse clinical outcomes. Selective ablation of pro-tumorgenic FAP+ stromal cells with CAR-T cells may be a new therapeutic strategy. However, the clinical use of FAP-CAR T cells is suggested to proceed with caution for occasional poor efficacy and induction of on-target off-tumor toxicity (OTOT), including lethal osteotoxicity and cachexia. Hence, more investigations and preclinical trials are required to optimize the FAP-CAR T cells and to approve their safety and efficacy.MethodsIn 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.ResultsResults 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.DiscussionTaken 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.

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Section: Resultsmentioning

confidence: 99%

“…HT1080, U87MG, 4T1 and Panc02 cell lines were preserved in our lab. hFAP-HT1080 cell line was constructed and preserved in our laboratory ( 16 ). mFAP-HT1080, mFAP-Panc02 cell lines were established accordingly by amplifying murine FAP from mouse skin tissue.…”

Section: Methodsmentioning

confidence: 99%