| Autor: |
Jiawei Fan, Ye Yu, Lanzhen Yan, Yuncang Yuan, Bin Sun, Dong Yang, Nan Liu, Jing Guo, Jie Zhang, Xudong Zhao |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Hematology & Oncology, Vol 16, Iss 1, Pp 1-17 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1756-8722 |
| DOI: |
10.1186/s13045-023-01467-9 |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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