Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody

Xianglei Liu; Doncho Zhelev; Cynthia Adams; Chuan Chen; John W Mellors; Dimiter S. Dimitrov

Translational Oncology (Dec 2021)

Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody

Xianglei Liu,
Doncho Zhelev,
Cynthia Adams,
Chuan Chen,
John W Mellors,
Dimiter S. Dimitrov

Affiliations

Xianglei Liu: Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, S843 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, United States; State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China; Corresponding author.
Doncho Zhelev: Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, S843 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, United States
Cynthia Adams: Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, S843 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, United States
Chuan Chen: Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, S843 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, United States
John W Mellors: Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, S843 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, United States; State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China
Dimiter S. Dimitrov: Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, S843 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, United States; Abound Bio, 1401 Forbes Ave, Pittsburgh, PA 15219, United States; Corresponding author.

Journal volume & issue: Vol. 14, no. 12
p. 101232

Abstract

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The pancaner molecule CD276 (B7-H3) is an attractive target for antibody based therapy. We identified from a large (1011) phage-displayed single-chain variable fragment (scFv) library, a fully human antibody, B11, which bound with high avidity (KD=0.4 nM) to CD276. B11 specifically bound to the V1/V2 domain of CD276 and competed with the antibody 8H9 (Omburtamab). It was used to design an IgG-format bispecific T cell engager B11-BiTE, which was more effective than 8H9-BiTE in 14 different cancer cell lines. B11-BiTE also exhibited strong ADCC/ADCP. Therefore, the fully human B11-BiTE is a promising candidate for treatment of tumors expressing CD276.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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