HER family targeted immunotherapy against head and neck squamous cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791735
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Asahikawa Medical College
• Principal Investigator: KUMAI Takumi 旭川医科大学, 医学部, 助教 (00596306)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 頭頸部癌 / 腫瘍免疫 / ペプチドワクチン療法 / EGFR / c-Met / ヘルパーT細胞 / EGFR阻害薬 / HLA

Outline of Final Research Achievements

T-cell-based immunotherapy has been proposed as a promising therapeutic approach to improve the clinical outcome for head and neck carcinoma (HNSCC).
In this study, we determined novel promiscuous EGFR epitopes that induced CD4 T-cell responses to HNSCC. The peptide-reactive CD4 T cells were capable of directly killing HNSCC cells. T cells reactive with the peptide could be detected in HNSCC patients. EGFR-reactive CD4 T cells were also able to recognise several peptide analogues derived from HER-2, HER-3 and c-Met. Finally, we examined the effects of EGFR inhibitors on CD4 T cell tumour reactivity. Treatment of tumour cells with the EGFR inhibitors enhanced tumour recognition by CD4 T cells presumably due to the upregulation of HLA-DR expression on the HNSCC cells.
These observations should facilitate the translation of T-cell-based immunotherapy into the clinic for the treatment of HNSCC and provide a rational basis for EGFR inhibition, immune-targeted combination therapy.

Free Research Field

頭頸部癌