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B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer

B7-H3 is an attractive target for immunotherapy because of its high expression across multiple solid tumors, including prostate cancer, and restricted expression in normal tissues. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable succe...

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Autores principales: Li, Shibao, Zhang, Miaomiao, Wang, Meng, Wang, Haiting, Wu, Han, Mao, Lijun, Zhang, Meng, Li, Huizhong, Zheng, Junnian, Ma, Ping, Wang, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164129/
https://www.ncbi.nlm.nih.gov/pubmed/37149721
http://dx.doi.org/10.1038/s41420-023-01453-7
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author Li, Shibao
Zhang, Miaomiao
Wang, Meng
Wang, Haiting
Wu, Han
Mao, Lijun
Zhang, Meng
Li, Huizhong
Zheng, Junnian
Ma, Ping
Wang, Gang
author_facet Li, Shibao
Zhang, Miaomiao
Wang, Meng
Wang, Haiting
Wu, Han
Mao, Lijun
Zhang, Meng
Li, Huizhong
Zheng, Junnian
Ma, Ping
Wang, Gang
author_sort Li, Shibao
collection PubMed
description B7-H3 is an attractive target for immunotherapy because of its high expression across multiple solid tumors, including prostate cancer, and restricted expression in normal tissues. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematological tumors. However, the potency of CAR-T cell therapy in solid tumors is still limited. Here, we examined the expression of B7-H3 in prostate cancer tissues and cells and developed a second-generation CAR that specifically targets B7-H3 and CD28 as costimulatory receptor to explore its tumoricidal potential against prostate cancer in vitro and in vivo. The high expression of B7-H3 was detected on both the surface of PC3, DU145 and LNCaP cells and prostate cancer tissues. B7-H3 CAR-T cells efficiently controlled the growth of prostate cancer in an antigen-dependent manner in vitro and in vivo. Moreover, tumor cells could induce the proliferation of CAR-T cells and the release of high levels of cytokines of IFN-γ and TNF-α in vitro. Results demonstrated that B7-H3 is a potential target for prostate cancer therapy that supports the clinical development of B7-H3 specific CAR-T cells for prostate cancer.
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spelling pubmed-101641292023-05-08 B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer Li, Shibao Zhang, Miaomiao Wang, Meng Wang, Haiting Wu, Han Mao, Lijun Zhang, Meng Li, Huizhong Zheng, Junnian Ma, Ping Wang, Gang Cell Death Discov Article B7-H3 is an attractive target for immunotherapy because of its high expression across multiple solid tumors, including prostate cancer, and restricted expression in normal tissues. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematological tumors. However, the potency of CAR-T cell therapy in solid tumors is still limited. Here, we examined the expression of B7-H3 in prostate cancer tissues and cells and developed a second-generation CAR that specifically targets B7-H3 and CD28 as costimulatory receptor to explore its tumoricidal potential against prostate cancer in vitro and in vivo. The high expression of B7-H3 was detected on both the surface of PC3, DU145 and LNCaP cells and prostate cancer tissues. B7-H3 CAR-T cells efficiently controlled the growth of prostate cancer in an antigen-dependent manner in vitro and in vivo. Moreover, tumor cells could induce the proliferation of CAR-T cells and the release of high levels of cytokines of IFN-γ and TNF-α in vitro. Results demonstrated that B7-H3 is a potential target for prostate cancer therapy that supports the clinical development of B7-H3 specific CAR-T cells for prostate cancer. Nature Publishing Group UK 2023-05-06 /pmc/articles/PMC10164129/ /pubmed/37149721 http://dx.doi.org/10.1038/s41420-023-01453-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Shibao
Zhang, Miaomiao
Wang, Meng
Wang, Haiting
Wu, Han
Mao, Lijun
Zhang, Meng
Li, Huizhong
Zheng, Junnian
Ma, Ping
Wang, Gang
B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer
title B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer
title_full B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer
title_fullStr B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer
title_full_unstemmed B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer
title_short B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer
title_sort b7-h3 specific car-t cells exhibit potent activity against prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164129/
https://www.ncbi.nlm.nih.gov/pubmed/37149721
http://dx.doi.org/10.1038/s41420-023-01453-7
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