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Development of a Tetravalent T-Cell Engaging Bispecific Antibody Against Glypican-3 for Hepatocellular Carcinoma.
- 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.)
- Subjects :
- Animals
CD3 Complex immunology
Cell Line
Cell Line, Tumor
Female
HEK293 Cells
Hep G2 Cells
Humans
Leukocytes, Mononuclear immunology
Mice
Xenograft Model Antitumor Assays methods
Antibodies, Bispecific immunology
Carcinoma, Hepatocellular immunology
Glypicans immunology
Liver Neoplasms immunology
T-Lymphocytes immunology
Subjects
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