Glypican 3型
癌症研究
抗原
免疫检查点
肝细胞癌
嵌合抗原受体
化学
T细胞
免疫疗法
外周血单个核细胞
抗体
体外
医学
单克隆抗体
双特异性抗体
免疫系统
免疫学
生物化学
作者
Yan‐Hui Lin,Nan Huang,Heng Sun,Xi Yang,Yuna Fu,Qiaoli Lang,Jianhua Wang,Liangpeng Ge
出处
期刊:Journal of Immunotherapy
[Ovid Technologies (Wolters Kluwer)]
日期:2020-11-24
卷期号:44 (3): 106-113
被引量:6
标识
DOI:10.1097/cji.0000000000000349
摘要
Cancer therapies benefit from accelerated development of biotechnology, and many immunotherapeutic strategies spring up including vaccines, the immune checkpoint blockade, chimeric antigen receptor T cells, and bispecific antibodies (BsAbs). Glypican-3 (GPC3) is a member of the heparan sulfate proteoglycan family of proteins and is highly expressed in hepatocellular carcinoma (HCC) cell membranes. Here, the authors describe a new tetravalent BsAb h8B-BsAb targeting GPC3 and CD3 antigens and studied its antitumor activities against HCC. h8B-BsAb was designed based on immunoglobulin G with a fragment variable fused to the light chain, whose biophysical stabilities including degradation resistance and thermostability were improved by introducing disulfide bonds. In vitro activity of h8B-BsAb showed potent T-cell recruitment and activation for HCC cell lysis by the presence of peripheral blood mononuclear cells, but no specific killing in GPC3-negative cells. In HCC xenograft mouse studies, h8B-BsAb induced robust regression of tumors. In summary, we engineered a highly stable and efficacious BsAb as a potential candidate for HCC treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI