| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
We evaluated the capacity of predicted CD4 T-cell peptide epitopes from HER family to induce anti-tumor immune responses. Among several predicted peptide epitopes, EGFR875-889 elicited CD4 T cell responses that were restricted by several HLA-DR alleles, indicating that the peptide functions as a promiscuous T cell epitope. The CD4 T cells were capable of directly recognized and killed HNSCC or lymphoma cells expressing antigens. Finally, we examined whether an EGFR tyrosine kinase inhibitor would affect CD4 T cell tumor reactivity. Treatment of tumor cells with the EGFR inhibitors enhanced tumor recognition by EGFR875-889 reactive T cells presumably due to the up-regulation of HLA-DR expression in the tumor cells. The results demonstrate the utility of EGFR inhibitors as immune modulators. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of maligancies and rational explanation for immune-targeted combination therapy.
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