靶向VEGFR2的融合抗体增强了自然杀伤细胞介导的对K562细胞的免疫监视。
VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells.
作者信息
Ren Xueyan, Xie Wei, Wang Youfu, Xu Menghuai, Liu Fang, Tang Mingying, Li Chenchen, Wang Min, Zhang Juan
机构信息
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 154#, Tong Jia Xiang 24, Nanjing, 210009, People's Republic of China.
出版信息
Immunol Res. 2016 Aug;64(4):1060-70. doi: 10.1007/s12026-016-8800-3.
MHC class I polypeptide-related sequence A (MICA), which is normally expressed on cancer cells, activates NK cells via NK group 2-member D pathway. However, some cancer cells escape NK-mediated immune surveillance by shedding membrane MICA causing immune suppression. To address this issue, we designed an antibody-MICA fusion targeting tumor-specific antigen (vascular endothelial growth factor receptor 2, VEGFR2) based on our patented antibody (mAb04) against VEGFR2. In vitro results demonstrate that the fusion antibody retains both the antineoplastic and the immunomodulatory activity of mAb04. Further, we revealed that it enhanced NK-mediated immunosurveillance against K562 cells through increasing degranulation and cytokine production of NK cells. The overall data suggest our new fusion protein provides a promising approach for cancer-targeted immunotherapy and has prospects for potential application of chronic myeloid leukemia.
主要组织相容性复合体I类多肽相关序列A（MICA）通常在癌细胞上表达，它通过自然杀伤细胞2组成员D途径激活自然杀伤细胞（NK细胞）。然而，一些癌细胞通过脱落膜型MICA逃避NK细胞介导的免疫监视，从而导致免疫抑制。为了解决这个问题，我们基于我们针对血管内皮生长因子受体2（VEGFR2）的专利抗体（单克隆抗体04，mAb04）设计了一种靶向肿瘤特异性抗原（VEGFR2）的抗体-MICA融合蛋白。体外实验结果表明，该融合抗体保留了mAb04的抗肿瘤和免疫调节活性。此外，我们发现它通过增加NK细胞的脱颗粒和细胞因子产生，增强了NK细胞介导的针对K562细胞的免疫监视。总体数据表明，我们的新型融合蛋白为癌症靶向免疫治疗提供了一种有前景的方法，并且在慢性髓性白血病的潜在应用方面具有前景。
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