Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer.
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.
Tsuruma
Tetsuhiro
T
Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. tsuruma@sapmed.ac.jp
Hata
Fumitake
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Torigoe
Toshihiko
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Furuhata
Tomohisa
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Idenoue
Satomi
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Kurotaki
Takehiro
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Yamamoto
Masaaki
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Yagihashi
Atsuhito
A
Ohmura
Tosei
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Yamaguchi
Koji
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Katsuramaki
Tadashi
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Yasoshima
Takahiro
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Sasaki
Kazuaki
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Mizushima
Yasuhiro
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Minamida
Hidetoshi
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Kimura
Hiromichi
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Akiyama
Morifumi
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Hirohashi
Yoshihiko
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Asanuma
Hiroko
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Tamura
Yasuaki
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Shimozawa
Kumiko
K
Sato
Noriyuki
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Hirata
Koichi
K