One of the problems in antigen-specific cancer immunotherapy is the low density of the tumor antigen-derived peptide endogenously presented on tumor cell surface major histocompatibility complex class I molecules. To overcome this, we are engaged in research on peptide intra-tumor injection to enhance tumor cell antigenicity. In in vivo studies using immunodeficient mice, the peptide injected into a solid mass of subcutaneous tumor was revealed to be loaded onto human leukocyte antigen class I molecules of tumor cells. In a peptide vaccine model and an adoptive cell transfer model using C57BL/6 mice, peptide intra-tumor injection was effective in terms of tumor growth inhibition and prolongation of survival time. Moreover, an antigen-spreading effect was detected after peptide intra-tumor injection. Peptide intra-tumor injection is an effective method of enhancing tumor cell antigenicity. It can induce additional peptide loading onto tumor cells, making tumor cells more antigenic for specific cytotoxic T-lymphocyte activity. Peptide intra-tumor injection may be a useful option for improvement of antigen-specific immunotherapy against solid tumors.
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