State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
Cancer Lett. 2016 Mar 28;372(2):166-78. doi: 10.1016/j.canlet.2016.01.001. Epub 2016 Jan 11.
MHC class I-related chain A (MICA) is a principal immunoligand of the natural killer (NK) cell receptor NK group 2, member D (NKG2D) and plays a key role in NK cell-mediated immune recognition. Shedding of MICA from tumor cells leads to immunosuppression. To reconstitute the immunosurveilance function of NK cells, we constructed a fusion protein rG7S-MICA and explored its potential anti-tumor activity against hepatocellular carcinoma (HCC). rG7S-MICA consists of human MICA and a single-chain antibody fragment (scFv) targeting the tumor-associated antigen cluster of differentiation 24 (CD24). In vitro, rG7S-MICA engaged both NK cells and CD24(+) human HCC cells, and triggered NK cell-mediated cytolysis. Furthermore, in CD24(+) HCC-bearing nude mice, rG7S-MICA specifically targeted to the tumor tissue, where it effectively recruited NK cells and induced the release of cytokines, and showed superior anti-tumor activity. In conclusion, rG7S-MICA provides a new approach for HCC-targeting immunotherapy and has attracting potentials for clinical applications.
主要组织相容性复合体Ⅰ类相关链 A（MICA）是自然杀伤（NK）细胞受体 NK 组 2 成员 D（NKG2D）的主要免疫配体，在 NK 细胞介导的免疫识别中发挥关键作用。肿瘤细胞脱落的 MICA 可导致免疫抑制。为了重建 NK 细胞的免疫监视功能，我们构建了融合蛋白 rG7S-MICA，并探讨了其对肝癌（HCC）的潜在抗肿瘤活性。rG7S-MICA 由人 MICA 和针对肿瘤相关抗原 CD24 的单链抗体片段（scFv）组成。体外实验中，rG7S-MICA 可同时与 NK 细胞和 CD24(+)人 HCC 细胞结合，并触发 NK 细胞介导的细胞溶解。此外，在 CD24(+) HCC 荷瘤裸鼠中，rG7S-MICA 可特异性靶向肿瘤组织，有效招募 NK 细胞并诱导细胞因子释放，显示出优异的抗肿瘤活性。总之，rG7S-MICA 为 HCC 靶向免疫治疗提供了一种新方法，具有吸引临床应用的潜力。
