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Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient

B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injecti...

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Autores principales: Hu, Gang, Li, Guangchao, Wen, Wei, Ding, Wen, Zhou, Zhao, Zheng, Yongwei, Huang, Taoyuan, Ren, Junnan, Chen, Rongyi, Zhu, Dingheng, He, Renliang, Liang, Yunsheng, Luo, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428555/
https://www.ncbi.nlm.nih.gov/pubmed/36059640
http://dx.doi.org/10.3389/fonc.2022.956593
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author Hu, Gang
Li, Guangchao
Wen, Wei
Ding, Wen
Zhou, Zhao
Zheng, Yongwei
Huang, Taoyuan
Ren, Junnan
Chen, Rongyi
Zhu, Dingheng
He, Renliang
Liang, Yunsheng
Luo, Min
author_facet Hu, Gang
Li, Guangchao
Wen, Wei
Ding, Wen
Zhou, Zhao
Zheng, Yongwei
Huang, Taoyuan
Ren, Junnan
Chen, Rongyi
Zhu, Dingheng
He, Renliang
Liang, Yunsheng
Luo, Min
author_sort Hu, Gang
collection PubMed
description B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region. Subsequently, high levels of TGF-β in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events. The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) with registration number ChiCTR2100044386.
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spelling pubmed-94285552022-09-01 Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient Hu, Gang Li, Guangchao Wen, Wei Ding, Wen Zhou, Zhao Zheng, Yongwei Huang, Taoyuan Ren, Junnan Chen, Rongyi Zhu, Dingheng He, Renliang Liang, Yunsheng Luo, Min Front Oncol Oncology B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region. Subsequently, high levels of TGF-β in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events. The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) with registration number ChiCTR2100044386. Frontiers Media S.A. 2022-08-17 /pmc/articles/PMC9428555/ /pubmed/36059640 http://dx.doi.org/10.3389/fonc.2022.956593 Text en Copyright © 2022 Hu, Li, Wen, Ding, Zhou, Zheng, Huang, Ren, Chen, Zhu, He, Liang and Luo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Hu, Gang
Li, Guangchao
Wen, Wei
Ding, Wen
Zhou, Zhao
Zheng, Yongwei
Huang, Taoyuan
Ren, Junnan
Chen, Rongyi
Zhu, Dingheng
He, Renliang
Liang, Yunsheng
Luo, Min
Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient
title Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient
title_full Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient
title_fullStr Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient
title_full_unstemmed Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient
title_short Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient
title_sort case report: b7-h3 car-t therapy partially controls tumor growth in a basal cell carcinoma patient
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428555/
https://www.ncbi.nlm.nih.gov/pubmed/36059640
http://dx.doi.org/10.3389/fonc.2022.956593
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