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

Zi Mei1, Kai Zhang2, Alfred King-Yin Lam3

  • 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Cancer Medicine
|December 5, 2019
PubMed

Insights

Chimeric antigen receptor (CAR)-T therapy shows promise for head and neck squamous cell carcinoma (HNSCC). CAR-T cells targeting MUC1, especially those secreting IL22, demonstrated enhanced antitumor activity in preclinical models.

Area of Science:

  • Immunotherapy
  • Oncology
  • Cellular Therapy

Background:

  • CAR-T therapy faces challenges in solid tumors like HNSCC due to tumor microenvironment and antigen loss.
  • MUC1 is a differentially expressed antigen in HNSCC, making it a potential therapeutic target.

Purpose of the Study:

  • To investigate the potential of CAR-T therapy for head and neck squamous cell carcinoma (HNSCC).
  • To evaluate MUC1 as a target antigen and the role of IL22 in enhancing CAR-T cell function against HNSCC.

Main Methods:

  • Selected MUC1 as the target antigen and verified its differential expression in HNSCC tissues.
  • Constructed second and fourth-generation CAR-T cells (CAR-MUC1 and CAR-MUC1-IL22).
  • Validated CAR-T cell cytotoxicity in vitro and antitumor efficacy in vivo.

Main Results:

  • Exogenous IL22 increased MUC1 expression and enhanced T cell function.
  • CAR-MUC1-IL22 T cells exhibited superior cytotoxic function against MUC1+ HNSCC cells in vitro and in vivo.
  • Demonstrated enhanced antitumor activity of CAR-MUC1-IL22 T cells compared to CAR-MUC1 T cells.

Conclusions:

  • CAR-T therapy targeting MUC1 holds significant potential for treating HNSCC.
  • The addition of IL22 secretion by CAR-T cells (CAR-MUC1-IL22) enhances therapeutic efficacy against MUC1+ HNSCC.
  • These findings provide a strong preclinical basis for MUC1-targeted CAR-T therapy in HNSCC patients.
Keywords:
CAR-TIL22MUC1head and neck squamous cell carcinoma

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