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

Authors
  • Mei, Zi1
  • Zhang, Kai2
  • Lam, Alfred King-Yin3
  • Huang, Junwen1
  • Qiu, Feng1
  • Qiao, Bin1
  • Zhang, Yi2
  • 1 Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. , (China)
  • 2 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. , (China)
  • 3 Cancer Molecular Pathology and Griffith Medical School, Griffith University, Gold Coast, Queensland, Australia. , (Australia)
Type
Published Article
Journal
Cancer Medicine
Publisher
Wiley
Publication Date
Dec 04, 2019
Identifiers
DOI: 10.1002/cam4.2733
PMID: 31800160
Source
Medline
Keywords
Language
English
License
Unknown

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 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. © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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