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Development of a Tetravalent T-Cell Engaging Bispecific Antibody Against Glypican-3 for Hepatocellular Carcinoma.

Authors :
Yu L
Huang N
Sun H
Yang X
Fu Y
Lang Q
Wang J
Ge L
Source :
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2021 Apr 01; Vol. 44 (3), pp. 106-113.
Publication Year :
2021

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.<br /> (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Details

Language :
English
ISSN :
1537-4513
Volume :
44
Issue :
3
Database :
MEDLINE
Journal :
Journal of immunotherapy (Hagerstown, Md. : 1997)
Publication Type :
Academic Journal
Accession number :
33239522
Full Text :
https://doi.org/10.1097/CJI.0000000000000349