Documentdetail
ID kaart
doi:10.1186/s13045-023-01467-9...
Auteur
Fan, Jiawei Yu, Ye Yan, Lanzhen Yuan, Yuncang Sun, Bin Yang, Dong Liu, Nan Guo, Jing Zhang, Jie Zhao, XudongLangue
enEditor
BioMed Central
Categorie
Medicine & Public Health
Jaar
2023
vermelding datum
26-07-2023
Trefwoorden
car-t-cell therapy tam family gas6 pancreatic cancer mice tam cancer pancreaticBeschrijving
Background The receptor tyrosine kinases TAM family (TYRO3, AXL, and MERTK) are highly expressed in multiple forms of cancer cells and tumor-associated macrophages and promote the development of cancers including pancreatic tumor.
Targeting TAM receptors could be a promising therapeutic option.
Methods We designed a novel CAR based on the extracellular domain of growth arrest-specific protein 6 (GAS6), a natural ligand for all TAM members.
The ability of CAR-T to kill pancreatic cancer cells is tested in vitro and in vivo, and the safety is evaluated in mice and nonhuman primate.
Results GAS6-CAR-T cells efficiently kill TAM-positive pancreatic cancer cell lines, gemcitabine-resistant cancer cells, and cancer stem-like cells in vitro.
GAS6-CAR-T cells also significantly suppressed the growth of PANC1 xenografts and patient-derived xenografts in mice.
Furthermore, these CAR-T cells did not induce obvious side effects in nonhuman primate or mice although the CAR was demonstrated to recognize mouse TAM.
Conclusions Our findings indicate that GAS6-CAR-T-cell therapy may be effective for pancreatic cancers with low toxicity.
Fan, Jiawei,Yu, Ye,Yan, Lanzhen,Yuan, Yuncang,Sun, Bin,Yang, Dong,Liu, Nan,Guo, Jing,Zhang, Jie,Zhao, Xudong, 2023, GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer, BioMed Central
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