Specific immunotherapy targeting MN/CA9 tumor-associated antigen for renal cell carcinoma

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MN/CA IX antigen is a plasma membrane glycoprotein expressed in several types of malignancies. Our previous study revealed that majority of renal cell carcinomas (RCC) express this antigen. We have synthesized 9mer antigen peptides and employed them as tumor vaccines to investigate the ability to induce this antiger specific responses. MN-RenCa and MN-3T3, MN/CA9 transfectant mouse renal cell carcinoma and embryofibroblast cell lines, have been established in our laboratory. Using these cell lines, we examined whether vaccination with the antigen peptides could induce specific CTL.Vaccines were made with HLA-A24 as well as H-2K^d restricted immunodominant peptides, and administrated into BALB/c mice with IFA every week. After the fourth vaccination, MN specific CTL activity was tested by TNF release assay and LDH release assay against MN-3T3. Furthermore, therapeutic efficacy of vaccination with the antigen peptides was investigated in syngeneic animal model. Spleen cells derived from BALB/c mouse vaccinated with antigen peptides showed reactivity against MN-RenCa and MN-3T3 cells, i.e., vaccination with MN antigen peptides resulted in the induction of MN specific CD8+ CTL precursor. This CTL precursor were transferred into naive mice after MN-RenCa inoculation and significantly low tumor-take was observed in these mice compared to control mice. These findings suggest that vaccination with MN antigen peptides may be potential therapeutic approach for RCC.