肿瘤细胞治疗研究
英文原题：Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant.
Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
利用先天免疫正成为肿瘤领域中一种有前景的治疗策略。
利用先天免疫正成为癌症治疗的一种有前景策略。我们报告了四特异性分子的设计，可同时结合自然杀伤（NK）细胞激活受体NKp46和CD16a、白细胞介素2受体（IL-2R）γ链及肿瘤相关抗原（TAA）。体外实验中，这类四特异性抗体型NK细胞连接器治疗药物（ANKET）可优先激活并促进NK细胞增殖；结合目标TAA后，会触发NK细胞细胞毒作用及细胞因子和趋化因子产生。体内实验中，四特异性ANKET诱导NK细胞增殖、在肿瘤部位蓄积，并控制局部及播散肿瘤。使用靶向CD20的四特异性ANKET治疗非人灵长类动物，可耗竭循环CD20+ B细胞，同时全身细胞因子释放极少且无毒性迹象。因此，四特异性ANKET构成一种技术平台，可利用NK细胞开发下一代癌症免疫疗法。
Harnessing innate immunity is emerging as a promising therapeutic approach in cancer. We report here the design of tetraspecific molecules engaging natural killer (NK) cell-activating receptors NKp46 and CD16a, the -chain of the interleukin-2 receptor (IL-2R), and a tumor-associated antigen (TAA). In vitro, these tetraspecific antibody-based natural killer cell engager therapeutics (ANKETs) induce a preferential activation and proliferation of NK cells, and the binding to the targeted TAA triggers NK cell cytotoxicity and cytokine and chemokine production. In vivo, tetraspecific ANKETs induce NK cell proliferation and their accumulation at the tumor bed, as well as the control of local and disseminated tumors. Treatment of non-human primates with CD20-directed tetraspecific ANKET leads to CD20 + circulating B cell depletion, with minimal systemic cytokine release and no sign of toxicity. Tetraspecific ANKETs, thus, constitute a technological platform for harnessing NK cells as next-generation cancer immunotherapies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
