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Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma

Takumi Kumai1,2,3, Takayuki Ohkuri1, Toshihiro Nagato2

  • 1Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.

Scientific Reports
|November 6, 2015
PubMed

Insights

This study identifies a HER-3 helper epitope for targeting head and neck cancer. This approach uses CD4 T cells to attack tumors, enhanced by HER-family inhibitors, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Therapy

Background:

  • HER-3 is an oncoprotein in head and neck squamous cell carcinoma.
  • HER-3 drives tumor proliferation and resistance to EGFR inhibitors.
  • Targeting HER-3 is a desirable therapeutic strategy.

Purpose of the Study:

  • To develop a novel HER-3-targeted therapy for HER-3-positive head and neck carcinoma.
  • To identify a HER-3 helper epitope that elicits effective T cell responses.
  • To evaluate the combination of HER-3 targeted therapy with HER-family inhibitors.

Main Methods:

  • Identification of a HER-3 helper epitope.
  • Assessment of CD4 T cell responses against HER-3 expressing tumor cells.
  • Evaluation of pan HER-family tyrosine kinase inhibitors on T cell responses and HLA-DR expression.

Main Results:

  • HER-3 expression increased after EGFR inhibition.
  • The identified HER-3 epitope induced potent CD4 T cell-mediated tumor cell killing.
  • Pan HER-family inhibitors augmented HER-3-reactive CD4 T cell responses by upregulating HLA-DR.

Conclusions:

  • CD4 T cell-dependent HER-3-targeted therapy is a valid approach for head and neck cancer.
  • Combining HER-3 targeted therapy with broad HER-family inhibitors shows therapeutic potential.

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