Active specific immunotherapy with MN\CA IX antigen peptide vaccines for renal cell carcinoma

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MN/CA IX antigen is a tumor-associated antigen expressed in approximately 90 % of renal cell carcinomas (RCQ). We have synthesized 9mer antigen peptides restricted to HLA-A24 and employed them as tumor vaccines to investigate the ability to induce this antigen specific responses in mouse syngeneic ROC model. Antigen specific CTL was induced by immunization of MN/CA9 9mer peptide vaccine in mouse system. This finding suggests that vaccination with MN/CA9 antigen peptides may be potential therapeutic approach for RCC patients. We also have investigated the capacity of CTL induction using RCC patient lymphocytes in vitro. In addition, presence of CTL precursor was investigated using PBMC from the patients with metastatic RCC patients. Stimulation of patient lymphocytes with autologons dendritic cell loaded MN/CA9 peptides resulted in antigen specific CTL induction.Based on these pie-clinical data, we started a phase-I study to investigate MN/CA9 peptide vaccines by subcutaneous administration in patients with disseminated renal cell carcinoma since July 2002. Patients with distant metastases received three sets of MN/CA9 9-mer peptide vaccines 6 times at 2-week intervals. Primary end points of this study are to evaluate the toxicity and immunogenicity of these antigen peptide vaccines. Six patients finished the protocol until now and only low grade toxicities such as fever, pruritus and local reaction (swelling, pain) were observed. Antigen specific cell-mediated cytotoxicity was induced in some patients. In addition, antibodies (IgG) against MN/CA9 peptides vaccines were detected in some patients. These findings suggest that our MN/CA9 peptide vaccines may be safe and applicable for HLA-A24 positive RCC patients. Moreover; we are currently investigating the generation of modified peptide vaccines to obtain more powerful antigenicity.