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Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody

OBJECTIVE: B7‐H3 is attractive for cancer immunotherapy with B7‐H3 overexpressed tumors. To explore whether B7‐H3 is an effective target for patients with bladder cancer, anti‐CD3× anti‐B7‐H3 bispecific antibodies (B7‐H3Bi‐Ab) was armed with activated T cells (ATC) to kill bladder cancer cells. METH...

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Autores principales: Ma, Wanru, Ma, Juan, Ma, Ping, Lei, Ting, Zhao, Man, Zhang, Man
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198238/
https://www.ncbi.nlm.nih.gov/pubmed/30253078
http://dx.doi.org/10.1002/cam4.1775
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author Ma, Wanru
Ma, Juan
Ma, Ping
Lei, Ting
Zhao, Man
Zhang, Man
author_facet Ma, Wanru
Ma, Juan
Ma, Ping
Lei, Ting
Zhao, Man
Zhang, Man
author_sort Ma, Wanru
collection PubMed
description OBJECTIVE: B7‐H3 is attractive for cancer immunotherapy with B7‐H3 overexpressed tumors. To explore whether B7‐H3 is an effective target for patients with bladder cancer, anti‐CD3× anti‐B7‐H3 bispecific antibodies (B7‐H3Bi‐Ab) was armed with activated T cells (ATC) to kill bladder cancer cells. METHODS: High expressions of B7‐H3 on human bladder cancer cells were detected, including Pumc‐91 and T24 cells, and their chemotherapeutic drug‐resistant counterparts. ATC generated from healthy donors were stimulated with anti‐CD3 monoclonal antibody and interleukin‐2 (IL‐2) for 13 days. The ability of ATC armed with B7‐H3Bi‐Ab to kill bladder cancer cells was detected by flow cytometry, LDH, Elisa, and luciferase quantitative assay. Moreover, ATC generated from bladder cancer patients was armed with B7‐H3Bi‐Ab to verity the cell killing by the methods as previously described. RESULTS: Compared with unarmed ATC, a significant increased cytotoxicity of B7‐H3Bi‐Ab‐armed ATC against bladder cancer cells was discovered. The B7‐H3Bi‐Ab‐armed ATC secreted more IFN‐γ, TNF‐α, and expressed high levels of activation marker CD69. Interestingly, despite the presence of immunosuppression in patients and resistance in chemotherapeutic drug‐resistant cancer cell lines, B7‐H3Bi‐Ab‐armed ATC from patients with bladder cancer still showed significant cytotoxic activity against bladder cancer cells and their chemotherapeutic drug‐resistant counterparts. CONCLUSION: B7‐H3 is an effective target for bladder cancer. B7‐H3Bi‐Ab enhances the ability of ATC to kill bladder cancer cells. B7‐H3Bi‐Ab‐armed ATC is promisingly to provide a novel strategy for current bladder cancer therapy.
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spelling pubmed-61982382018-10-31 Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody Ma, Wanru Ma, Juan Ma, Ping Lei, Ting Zhao, Man Zhang, Man Cancer Med Cancer Biology OBJECTIVE: B7‐H3 is attractive for cancer immunotherapy with B7‐H3 overexpressed tumors. To explore whether B7‐H3 is an effective target for patients with bladder cancer, anti‐CD3× anti‐B7‐H3 bispecific antibodies (B7‐H3Bi‐Ab) was armed with activated T cells (ATC) to kill bladder cancer cells. METHODS: High expressions of B7‐H3 on human bladder cancer cells were detected, including Pumc‐91 and T24 cells, and their chemotherapeutic drug‐resistant counterparts. ATC generated from healthy donors were stimulated with anti‐CD3 monoclonal antibody and interleukin‐2 (IL‐2) for 13 days. The ability of ATC armed with B7‐H3Bi‐Ab to kill bladder cancer cells was detected by flow cytometry, LDH, Elisa, and luciferase quantitative assay. Moreover, ATC generated from bladder cancer patients was armed with B7‐H3Bi‐Ab to verity the cell killing by the methods as previously described. RESULTS: Compared with unarmed ATC, a significant increased cytotoxicity of B7‐H3Bi‐Ab‐armed ATC against bladder cancer cells was discovered. The B7‐H3Bi‐Ab‐armed ATC secreted more IFN‐γ, TNF‐α, and expressed high levels of activation marker CD69. Interestingly, despite the presence of immunosuppression in patients and resistance in chemotherapeutic drug‐resistant cancer cell lines, B7‐H3Bi‐Ab‐armed ATC from patients with bladder cancer still showed significant cytotoxic activity against bladder cancer cells and their chemotherapeutic drug‐resistant counterparts. CONCLUSION: B7‐H3 is an effective target for bladder cancer. B7‐H3Bi‐Ab enhances the ability of ATC to kill bladder cancer cells. B7‐H3Bi‐Ab‐armed ATC is promisingly to provide a novel strategy for current bladder cancer therapy. John Wiley and Sons Inc. 2018-09-25 /pmc/articles/PMC6198238/ /pubmed/30253078 http://dx.doi.org/10.1002/cam4.1775 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Ma, Wanru
Ma, Juan
Ma, Ping
Lei, Ting
Zhao, Man
Zhang, Man
Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody
title Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody
title_full Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody
title_fullStr Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody
title_full_unstemmed Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody
title_short Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody
title_sort targeting immunotherapy for bladder cancer using anti‐cd3× b7‐h3 bispecific antibody
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198238/
https://www.ncbi.nlm.nih.gov/pubmed/30253078
http://dx.doi.org/10.1002/cam4.1775
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