Construction of a novel TROP2/CD3 bispecific antibody with potent antitumor activity and reduced induction of Th1 cytokines.

Abstract

Many cancers, including triple-negative breast cancer, overexpress TROP2 on the surface of tumor cells. TROP2 has become a promising tumor associated antigen for the development of novel antibody-based targeted therapy. Herein, we constructed a novel bispecific antibody with the ability to simultaneously target TROP2 on the tumor surface and bind to CD3 to activate T cells. Given that the excessive production of Th1 cytokines induced by CD3-mediated T-cell overactivation may lead to toxicity in the clinic, we devised a strategy to modify this CD3-induced T cell activation by a two-step reduction in the bispecific antibody binding affinity for CD3 to a level that retained the ability of the bispecific antibody to effectively inhibit tumor growth while greatly reducing the amount of Th1 cytokines secreted by T cells. Thus, we provide insight into the design of T cell engagers that exhibit a promising toxicity profile while retaining inhibitory effects on tumor growth.

• Authors: Dinghe Wang, Lige Zhang, Baoli Wang, Le Zhao, Lan Deng, Wei Xu, Haomin Huang
• Journal: Protein expression and purification (Protein Expr Purif) Vol. 205 Pg. 106242 (05 2023) ISSN: 1096-0279 [Electronic] United States
• PMID: 36746324 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Bispecific
• CD3 Complex
• Cytokines
• Cell Adhesion Molecules
• Antigens, Neoplasm

Topics

• Humans
• Antibodies, Bispecific (genetics, pharmacology)
• CD3 Complex (metabolism)
• Cytokines (metabolism, pharmacology)
• Neoplasms (metabolism)
• T-Lymphocytes
• Xenograft Model Antitumor Assays
• Cell Adhesion Molecules (metabolism)
• Antigens, Neoplasm (metabolism)