9/4/2023 0 Comments Jing gao google scholar ncar![]() Receptor tyrosine kinase TAM (TYRO3, AXL, MERTK) family members are overexpressed in several hematological malignancies, including acute myeloid leukemia, chronic myeloid leukemia, and acute lymphoid leukemia, and in different types of solid tumors, such as pancreatic, lung, gastric, and breast cancers. However, current CAR-T cells targeting a range of different proteins have not shown remarkable efficacy against pancreatic cancer in clinical trials, indicating the need to explore more effective CAR-T strategies. In terms of new treatments, chimeric antigen receptor T (CAR-T) cell therapies have recently been shown to be highly successful for hematological malignancies, and this approach also shows promising results against solid tumors, including pancreatic cancers. Pancreatic cancer is the most lethal malignancy with less than 10% of patients surviving five years after diagnosis. Our findings indicate that GAS6-CAR-T-cell therapy may be effective for pancreatic cancers with low toxicity. 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. GAS6-CAR-T cells also significantly suppressed the growth of PANC1 xenografts and patient-derived xenografts in mice. GAS6-CAR-T cells efficiently kill TAM-positive pancreatic cancer cell lines, gemcitabine-resistant cancer cells, and cancer stem-like cells in vitro. 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. We designed a novel CAR based on the extracellular domain of growth arrest-specific protein 6 (GAS6), a natural ligand for all TAM members. Targeting TAM receptors could be a promising therapeutic option. 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. ![]()
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