Development of an Ideal and Potent Cancer Immunotherapy Designed by Consideration of HLA Polymorphism

概要

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To develop cancer immunotherapy, we identified the tumor-associated antigens (TAAs) that are prominently expressed only in cancer cells but not in normal tissues by using the genome-wide cDNA microarray analyses. TAA-derived peptides predicted in silico to be bound by frequent HLA class I molecules in the Japanese population were synthesized, and several peptides that could induce the HLA class I-restricted, TAA peptide-specific and tumor-reactive cytotoxic T lymphocyte (CTL) were identified by using HLA class I transgenic mice and human peripheral blood mononuclear cells. The phase I clinical trials of cancer immunotherapy using those TAA-derived peptides showed the safety and some effectiveness. To further improve the effectiveness of the TAA-targeted cancer immunotherapy, we identified TAA-derived peptides that can stimulate both TAA-specific CTL and helper T (Th) cells, and developed genetically modified allogeneic iPS cell-derived dendritic cell-mediated immunotherapy that can overcome the potential problems of histoincompatibility between iPS cell donors and cancer patients.
Japanese Society for Histocompatibility and Immunogeneticsの論文