NKG2D公司
抗体
癌症研究
免疫系统
免疫疗法
MHC I级
免疫学
细胞毒性
主要组织相容性复合体
体外
化学
生物
生物化学
作者
Yang Wang,Hui Li,Wei Xü,Mingzhu Pan,Chun Qiao,Jialing Cai,Jingjing Xu,Min Wang,Juan Zhang
出处
期刊:Journal of Immunotherapy
[Ovid Technologies (Wolters Kluwer)]
日期:2020-04-28
卷期号:43 (6): 175-188
被引量:28
标识
DOI:10.1097/cji.0000000000000320
摘要
B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein expressed on malignant plasma cells of patients with multiple myeloma (MM), and it is a defined therapeutic target. Major histocompatibility complex class I-related chain A (MICA) is frequently expressed in lymphoproliferative malignancies including MM. MICA activates natural killer (NK) cells and costimulates T cells by interaction with its immunoreceptor NK cell receptor G2D (NKG2D). Nonetheless, during full-blown MM, tumor cells promote efficient MICA shedding, which evokes NKG2D internalization and immune suppression. To enhance the directional killing efficacy of immune cells against myeloma cells, we constructed a novel bispecific antibody 2A9-MICA and explored its potential antimyeloma activity against MM. 2A9-MICA consists of human MICA extracellular region and a single–chain antibody fragment (scFv) that targets BCMA generated by phage display technology. In vitro, 2A9-MICA activated NK cell-mediated cytotoxicity and induced NK cells to kill BCMA–positive human myeloma cells. Moreover, in BCMA-positive, MM-bearing nude mice, 2A9-MICA specifically targeted tumor tissue, where it effectively recruited immune cells and inhibited tumor tissue growth showed superior antitumor activity. Taken together, bispecific antibody 2A9-MICA provides a new approach for MM-targeting immunotherapy and has attractive potential for clinical applications.
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