Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China.
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Methods Mol Biol. 2021;2388:175-180. doi: 10.1007/978-1-0716-1775-5_16.
Invariant natural killer T (iNKT) cells display important properties that could bridge the innate and adaptive immunity, and they have been shown to play key roles in cancer immunotherapy. However, administration of iNKT cell agonist αGalCer fails to induce sustained antitumor immunity due to the rapid anergy induction after an initial strong activation. To this end, we have designed a recombinant CD1d protein that is fused to an anti-TAA scFv, which is able to recruit iNKT cells to the tumor site and induce tumor regression. Importantly, recombinant CD1d fusion proteins loaded with α-GalCer demonstrated sustained activation of iNKT cells upon repeated injections and superior tumor control, as compared to α-GalCer treatment.
不变自然杀伤 T(iNKT)细胞表现出重要的特性，可以连接先天免疫和适应性免疫，并且已经证明它们在癌症免疫治疗中发挥关键作用。然而，由于初始强烈激活后快速失能诱导，施用 iNKT 细胞激动剂 αGalCer 未能诱导持续的抗肿瘤免疫。为此，我们设计了一种与抗 TAA scFv 融合的重组 CD1d 蛋白，能够将 iNKT 细胞募集到肿瘤部位并诱导肿瘤消退。重要的是，与 α-GalCer 处理相比，负载 α-GalCer 的重组 CD1d 融合蛋白重复注射时能够持续激活 iNKT 细胞，并具有更好的肿瘤控制效果。
