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

The pancaner molecule CD276 (B7-H3) is an attractive target for antibody based therapy. We identified from a large (10(11)) phage-displayed single-chain variable fragment (scFv) library, a fully human antibody, B11, which bound with high avidity (K(D)=0.4 nM) to CD276. B11 specifically bound to the...

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Detalles Bibliográficos
Autores principales: Liu, Xianglei, Zhelev, Doncho, Adams, Cynthia, Chen, Chuan, Mellors, John W, Dimitrov, Dimiter S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Original Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493583/
https://www.ncbi.nlm.nih.gov/pubmed/34601396
http://dx.doi.org/10.1016/j.tranon.2021.101232
Descripción
Sumario:The pancaner molecule CD276 (B7-H3) is an attractive target for antibody based therapy. We identified from a large (10(11)) phage-displayed single-chain variable fragment (scFv) library, a fully human antibody, B11, which bound with high avidity (K(D)=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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