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靶向DNAM-1的嵌合抗原受体增强效应T细胞的功能和抑制体内抗黑色素瘤

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发表于 2016-1-27 21:45:42 | 显示全部楼层 |阅读模式
dnaM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma.
Chimeric antigen receptor (CAR) T cell therapies hold great potential for treating cancers, and new CARs that can target multiple tumor types and have the potential to target non-hematological malignancies are needed. In this study, the tumor recognition ability of a natural killer cell-activating receptor, DNAM-1 was harnessed to design CARs that target multiple tumor types. DNAM-1 ligands, PVR and nectin-2, are expressed on primary human leukemia, myeloma, ovarian cancer, melanoma, neuroblastoma, and Ewing sarcoma. DNAM-1 CARs exhibit high tumor cell cytotoxicity but low IFN-γ secretion in vitro. In contrast to other CAR designs, co-stimulatory domains did not improve the expression and function of DNAM-1 CARs. A DNAM-1/CD3zeta CAR reduced tumor burden in a murine melanoma model in vivo. In conclusion, DNAM-1-based CARs may have the potential to treat PVR and nectin-2 expressing hematological and solid tumors.
靶向DNAM-1的嵌合抗原受体增强效应T细胞的功能和抑制体内抗黑色素瘤
CAR-T细胞治疗对于癌症有强大的治疗潜力,新的CAR 能够靶向多种肿瘤类型,并且具有靶向非血液系统恶性肿瘤的潜能。在这篇文章中,一种自然杀伤细胞活化受体DNAM-1的识别肿瘤的能力,被用来设计靶向多种肿瘤的CARDNAM-1配体,PVRNectin-2主要在人类白血病、骨髓瘤、卵巢癌、黑色素瘤、神经母细胞瘤、Ewing肉瘤细胞中表达。DNAM-1 CAR具有较高的肿瘤细胞的细胞毒性、较低的体外分泌IFN-γ的能力。与其他的CAR设计相比,共刺激域并未改善DNAM-1-CAR的表达和功能。一种DNAM-1 / CD3zetaCAR减少小鼠黑色素瘤体内模型的肿瘤负担。总之,DNAM-1为基础的CAR可能有治疗表达PVR Nectin-2的血液系统肿瘤和实体瘤的潜力。
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