Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer

摘要

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34‐kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil‐tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination‐induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA‐masked fashion. After the disclosure of HLA, 28 patients were in the HLA‐A*2402‐matched and 16 were in the unmatched group. In the HLA‐matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA‐unmatched group, 10 CTL responses were positive and 2 negative. In the HLA‐matched group, 3‐year relapse‐free survival ( style="fixed-case">RFS) was significantly better in the positive style="fixed-case">CTL subgroup than in the negative‐response subgroup. Patients with negative vaccination‐induced style="fixed-case">CTL responses showed a significant trend towards shorter style="fixed-case">RFS than those with positive responses. Moreover, in the style="fixed-case">HLA‐unmatched group, the positive style="fixed-case">CTL response subgroup showed an equally good 3‐year style="fixed-case">RFS as in the style="fixed-case">HLA‐matched group. In conclusion, vaccination‐induced style="fixed-case">CTL response to peptide vaccination could predict survival in the adjuvant setting for stage style="fixed-case">III CRC.