Open AccessMUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
Author(s) -
Mei Zi,
Zhang Kai,
Lam Alfred KingYin,
Huang Junwen,
Qiu Feng,
Qiao Bin,
Zhang Yi
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2733
Subject(s) - muc1 , chimeric antigen receptor , cytotoxic t cell , head and neck squamous cell carcinoma , cancer research , immunotherapy , in vitro , in vivo , head and neck cancer , cancer , cytotoxicity , antigen , medicine , immunology , biology , biochemistry , microbiology and biotechnology
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.