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...

Descripción completa

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
_version_ 1784579148580126720
author Liu, Xianglei
Zhelev, Doncho
Adams, Cynthia
Chen, Chuan
Mellors, John W
Dimitrov, Dimiter S.
author_facet Liu, Xianglei
Zhelev, Doncho
Adams, Cynthia
Chen, Chuan
Mellors, John W
Dimitrov, Dimiter S.
author_sort Liu, Xianglei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8493583
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Neoplasia Press
record_format MEDLINE/PubMed
spelling pubmed-84935832021-10-14 Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody Liu, Xianglei Zhelev, Doncho Adams, Cynthia Chen, Chuan Mellors, John W Dimitrov, Dimiter S. Transl Oncol Original Research 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. Neoplasia Press 2021-10-01 /pmc/articles/PMC8493583/ /pubmed/34601396 http://dx.doi.org/10.1016/j.tranon.2021.101232 Text en Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Liu, Xianglei
Zhelev, Doncho
Adams, Cynthia
Chen, Chuan
Mellors, John W
Dimitrov, Dimiter S.
Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody
title Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody
title_full Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody
title_fullStr Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody
title_full_unstemmed Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody
title_short Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody
title_sort effective killing of cells expressing cd276 (b7-h3) by a bispecific t cell engager based on a new fully human antibody
topic Original Research
url 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
work_keys_str_mv AT liuxianglei effectivekillingofcellsexpressingcd276b7h3byabispecifictcellengagerbasedonanewfullyhumanantibody
AT zhelevdoncho effectivekillingofcellsexpressingcd276b7h3byabispecifictcellengagerbasedonanewfullyhumanantibody
AT adamscynthia effectivekillingofcellsexpressingcd276b7h3byabispecifictcellengagerbasedonanewfullyhumanantibody
AT chenchuan effectivekillingofcellsexpressingcd276b7h3byabispecifictcellengagerbasedonanewfullyhumanantibody
AT mellorsjohnw effectivekillingofcellsexpressingcd276b7h3byabispecifictcellengagerbasedonanewfullyhumanantibody
AT dimitrovdimiters effectivekillingofcellsexpressingcd276b7h3byabispecifictcellengagerbasedonanewfullyhumanantibody

Ejemplares similares