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B7H6特异性嵌合抗原受体导致肿瘤的消除和宿主的抗肿瘤免疫

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发表于 2016-1-27 14:06:42 | 显示全部楼层 |阅读模式
B7H6-specific chimeric antigen receptors lead to tumor elimination and host antitumor immunity.
Chimeric antigen receptor (CAR) T-cell therapies have demonstrated durable and potentially curative therapeutic efficacy against B-cell leukemia in clinical trials. A CAR strategy can target any tumor surface antigens as long as an antigen-binding receptor can be generated. New CARs that target solid tumors and have the potential to target multiple tumor types are needed. In this study, B7H6, a ligand for the NK cell activating receptor NKp30, was targeted to create a CAR that targets multiple tumor types. B7H6 is expressed on various primary human tumors, including leukemia, lymphoma and gastrointestinal stromal tumors, but it is not constitutively expressed on normal tissues. B7H6-specific CAR T cells have robust cellular cytotoxicity and interferon-γ secretion when co-cultured with B7H6+ tumor cells, and they exhibit little self-reactivity to immature dendritic cells or pro-inflammatory monocytes. In vivo, B7H6-specific CAR T cells greatly enhanced the survival of RMA/B7H6 lymphoma-bearing mice. The long-term survivor mice were protected against a B7H6-deficient tumor re-challenge. This CAR therapy also decreased tumor burden in a murine ovarian cancer model. In conclusion, B7H6-specific CARs have the potential to treat B7H6+ hematologic and solid tumors.
B7H6特异性嵌合抗原受体导致肿瘤的消除和宿主的抗肿瘤免疫
嵌合抗原受体(CAR)修饰的T细胞治疗对于B细胞白血病已经显示了长期有效的治疗效果。只要可以产生抗原结合的受体,理论上CAR-T能够针对肿瘤表面的任何抗原。新的能够靶向实体肿瘤和具有靶向多种癌症潜能的CARs是目前需要的。在这个研究中,B7H6分子,NK细胞活化的受体的配体,能够有针对性的靶向多种癌症细胞。B7H6表达于各种原发性肿瘤,包括白血病、淋巴瘤、胃肠道间质瘤,但它不是正常组织的组成性表达。B7H6特异性CAR-T细胞具有强大的细胞毒性,当与B7H6+肿瘤细胞共培养时,能够分泌干扰素γ,它们对于未成熟树突状细胞或炎性细胞很少有自反应性。体内试验中,B7H6特异性CAR-T细胞增强了RMAb7h6淋巴瘤小鼠的存活率。在小鼠卵巢癌模型中,这种CAR-T治疗方案也能减少肿瘤带来的负担。总之,B7H6特异性CAR-T具有对抗B7H6+血液和实体肿瘤的潜力。
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