Non-human primates are widely used in medical researches including development of vaccines against pathogens, because their immune system is similar to that in humans. In particular, the Old World monkeys such as rhesus macaques (Macaca mulatta) and cynomolgus macaques (crab-eating macaques, Macaca fascicularis) are useful models for human infectious diseases, especially for developing a strategy for vaccination against HIV, by using simian immunodeficiency virus (SIV) infection as a model system. Because there are individual differences in immune responsiveness, which are controlled by the polymorphic nature of the major histocompatibility (MHC) locus, it is important to reveal the diversity of MHC in the model animal. We analyzed polymorphisms in Mhc class I loci in rhesus macaques (Mamu locus) from Myanmar (Burma) and Laos and cynomolgus macaques (Mafa locus) from Indonesia, Malaysia and Philippine to obtain genetic information about the role of Mhc class I diversity in the immune responsiveness. We found that each Mhc class I haplotype was composed of one to three Mamu-A or Mafa-A alleles and one to five Mamu-B or Mafa-B alleles. In addition, family studies revealed that there were three Mhc haplotypes carrying two Mhc-A1 alleles not only in rhesus but also in cynomolgus macaques. These observations further demonstrated the complexity of Mhc class I loci in the Old World monkeys.

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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.

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