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

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 immunolo...

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Detalles Bibliográficos
Autores principales: Kawamura, Junichiro, Sugiura, Fumiaki, Sukegawa, Yasushi, Yoshioka, Yasumasa, Hida, Jin‐ichi, Hazama, Shoichi, Okuno, Kiyotaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980387/
https://www.ncbi.nlm.nih.gov/pubmed/29473265
http://dx.doi.org/10.1111/cas.13547
Descripción
Sumario: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 (RFS) was significantly better in the positive CTL subgroup than in the negative‐response subgroup. Patients with negative vaccination‐induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA‐unmatched group, the positive CTL response subgroup showed an equally good 3‐year RFS as in the HLA‐matched group. In conclusion, vaccination‐induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC.