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MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

The modification of chimeric antigen receptor (CAR) endowing T cells with tumor‐specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors...

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Detalles Bibliográficos
Autores principales: Mei, Zi, Zhang, Kai, Lam, Alfred King‐Yin, Huang, Junwen, Qiu, Feng, Qiao, Bin, Zhang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970025/
https://www.ncbi.nlm.nih.gov/pubmed/31800160
http://dx.doi.org/10.1002/cam4.2733
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author Mei, Zi
Zhang, Kai
Lam, Alfred King‐Yin
Huang, Junwen
Qiu, Feng
Qiao, Bin
Zhang, Yi
author_facet Mei, Zi
Zhang, Kai
Lam, Alfred King‐Yin
Huang, Junwen
Qiu, Feng
Qiao, Bin
Zhang, Yi
author_sort Mei, Zi
collection PubMed
description The modification of chimeric antigen receptor (CAR) endowing T cells with tumor‐specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR‐T therapy. The purpose of our study was to find and verify the potentials of CAR‐T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non‐neoplastic tissues (ANNT). Next, we constructed a second‐generation CAR and validated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth‐generation CAR that secretes IL22. Finally, we verified the antitumor function of two different CAR‐T cells in vitro and in vivo, respectively. CAR‐MUC1‐IL22 T cells were found to have a stronger and more effective cytotoxic function against MUC1 + HNSCC cells. Taken together, these results demonstrate the potential effectiveness of CAR‐T in the treatment of patients with HNSCC and provide evidence‐based of MUC1 + CAR‐T therapy.
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spelling pubmed-69700252020-01-27 MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma Mei, Zi Zhang, Kai Lam, Alfred King‐Yin Huang, Junwen Qiu, Feng Qiao, Bin Zhang, Yi Cancer Med Clinical Cancer Research The modification of chimeric antigen receptor (CAR) endowing T cells with tumor‐specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR‐T therapy. The purpose of our study was to find and verify the potentials of CAR‐T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non‐neoplastic tissues (ANNT). Next, we constructed a second‐generation CAR and validated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth‐generation CAR that secretes IL22. Finally, we verified the antitumor function of two different CAR‐T cells in vitro and in vivo, respectively. CAR‐MUC1‐IL22 T cells were found to have a stronger and more effective cytotoxic function against MUC1 + HNSCC cells. Taken together, these results demonstrate the potential effectiveness of CAR‐T in the treatment of patients with HNSCC and provide evidence‐based of MUC1 + CAR‐T therapy. John Wiley and Sons Inc. 2019-12-04 /pmc/articles/PMC6970025/ /pubmed/31800160 http://dx.doi.org/10.1002/cam4.2733 Text en © 2019 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 Clinical Cancer Research
Mei, Zi
Zhang, Kai
Lam, Alfred King‐Yin
Huang, Junwen
Qiu, Feng
Qiao, Bin
Zhang, Yi
MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
title MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
title_full MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
title_fullStr MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
title_full_unstemmed MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
title_short MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
title_sort muc1 as a target for car‐t therapy in head and neck squamous cell carinoma
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970025/
https://www.ncbi.nlm.nih.gov/pubmed/31800160
http://dx.doi.org/10.1002/cam4.2733
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