Development new generation peptides derived from CA9 as tailar-made vaccines for renal cell carcinoma

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We have previously developed 3 CA9-derived peptide vaccines (CA9p219, p288, p323) having the ability to induce HLA-A2402 restricted CA9 specific CTL. Recently a phase-I peptide vaccination trial was carried out in 23 patients with cytokine refractory RCC patients, and resulted in promising efficacy without any major adverse events. However, more than 3 months were needed for induction of specific CTL and more than 6 months were needed for clinical responses. This may be due to relatively low immunogenic peptides. The aim of our study is to develop more immunogenic new peptide vaccines having the higher ability to induce CA9-specific CTL response. We made 25 kinds of CA9 9mer peptides including modified peptides of CA9p219 and CA9p288, and checked their affinity to HLA-A24 molecule by MHC stabilization assay. Surprisingly, CA9p219 had a low affinity although it has high affinity estimation by the computer software and actually had the highest ability of CTL induction in the clinical trial, indicating that real affinity is not associated with the affinity estimation. Based on these data, we screened all peptide made in this study whether these peptides could induce CA9 specific CTL responses. We found several peptides have the higher ability to induce CA9 specific CTL responses. We are currently investigating direct killing capability to CA9 positive cancer cells (SW620) of these peptides.