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

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    Version of Record (VoR)
    Author(s)
    Mei, Zi
    Zhang, Kai
    Lam, Alfred King-Yin
    Huang, Junwen
    Qiu, Feng
    Qiao, Bin
    Zhang, Yi
    Griffith University Author(s)
    Lam, Alfred K.
    Year published
    2020
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    Abstract
    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 ...
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    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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    Journal Title
    Cancer Medicine
    DOI
    https://doi.org/10.1002/cam4.2733
    Copyright Statement
    © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
    Note
    This publication has been entered into Griffith Research Online as an Advanced Online Version.
    Subject
    Biochemistry and cell biology
    Oncology and carcinogenesis
    INFLAMMATION
    CARCINOMA
    CANCER
    IL-7
    INTERLEUKIN-22
    Publication URI
    http://hdl.handle.net/10072/389904
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    • Journal articles

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