Journal of Translational Medicine (Jun 2004)

Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

  • Minamida Hidetoshi,
  • Mizushima Yasuhiro,
  • Sasaki Kazuaki,
  • Yasoshima Takahiro,
  • Katsuramaki Tadashi,
  • Yamaguchi Koji,
  • Ohmura Tosei,
  • Yagihashi Atsuhito,
  • Yamamoto Masaaki,
  • Kurotaki Takehiro,
  • Idenoue Satomi,
  • Furuhata Tomohisa,
  • Torigoe Toshihiko,
  • Hata Fumitake,
  • Tsuruma Tetsuhiro,
  • Kimura Hiromichi,
  • Akiyama Morifumi,
  • Hirohashi Yoshihiko,
  • Asanuma Hiroko,
  • Tamura Yasuaki,
  • Shimozawa Kumiko,
  • Sato Noriyuki,
  • Hirata Koichi

DOI
https://doi.org/10.1186/1479-5876-2-19
Journal volume & issue
Vol. 2, no. 1
p. 19

Abstract

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Abstract Survivin is a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL) recognized by CD8+ cytotoxic T lymphocytes (CTLs). We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2), general malaise (grade 1), and fever (grade 1). No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9) decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.