Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody |
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| Authors: | Xianglei Liu Doncho Zhelev Cynthia Adams Chuan Chen John W Mellors Dimiter S. Dimitrov |
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| Affiliation: | 1. 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;3. Abound Bio, 1401 Forbes Ave, Pittsburgh, PA 15219, United States |
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| Abstract: | 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. |
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| Keywords: | Fully human antibody CD276 (B7-H3) V1/V2 domain Bispecific T cell engager (BiTE) |
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