Development of a Tetravalent T-Cell Engaging Bispecific Antibody Against Glypican-3 for Hepatocellular Carcinoma. Issue 3 (April 2021)

• Record Type: Journal Article
• Authors: Yu, Lin; Huang, Nan; Sun, Heng; Yang, Xi; Fu, Yuna; Lang, Qiaoli; Wang, Jianhua; Ge, Liangpeng
• Is Part Of: Journal of immunotherapy. Volume 44:Issue 3(2021)
• Publication Date: 2021-04
• Subjects: bispecific antibody -- hepatocellular carcinoma -- GPC3 -- CD3; Immunotherapy -- Periodicals; Immunotherapy -- Periodicals; Neoplasms -- therapy -- Periodicals; Electronic journals; Electronic journals; 615.37
• DOI: 10.1097/CJI.0000000000000349
• Languages: English
• ISSNs: 1524-9557

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.