Potential survival benefit of anti-apoptosis protein: survivin-derived peptide vaccine with and without interferon alpha therapy for patients with advanced or recurrent urothelial cancer--results from phase I clinical trials.

Abstract

We previously identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88, a member of the inhibitor of apoptosis protein family, recognized by CD8+cytotoxic T lymphocytes (CTL). In a phase I clinical trial of survivin-2B80-88 vaccination for metastatic urothelial cancer (MUC), we achieved clinical and immunological responses with safety. Moreover, our previous study indicated that interferon alpha (IFN α ) enhanced the effects of the vaccine for colorectal cancer. Therefore, we started a new phase I clinical trial of survivin-2B80-88 vaccination with IFN α for MUC patients. Twenty-one patients were enrolled and no severe adverse event was observed. HLA-A24/survivin-2B80-88 tetramer analysis and ELISPOT assay revealed a significant increase in the frequency of the peptide-specific CTLs after vaccination in nine patients. Six patients had stable disease. The effects of IFN α on the vaccination were unclear for MUC. Throughout two trials, 30 MUO patients received survivin-2B80-88 vaccination. Patients receiving the vaccination had significantly better overall survival than a comparable control group of MUO patients without vaccination (P = 0.0009). Survivin-2B80-88 vaccination may be a promising therapy for selected patients with MUC refractory to standard chemotherapy. This trial was registered with UMIN00005859.

• Authors: Toshiaki Tanaka, Hiroshi Kitamura, Ryuta Inoue, Sachiyo Nishida, Akari Takahashi-Takaya, Sachiyo Kawami, Toshihiko Torigoe, Yoshihiko Hirohashi, Taiji Tsukamoto, Noriyuki Sato, Naoya Masumori
• Journal: Clinical & developmental immunology (Clin Dev Immunol) Vol. 2013 Pg. 262967 ( 2013) ISSN: 1740-2530 [Electronic] Egypt
• PMID: 24363758 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BIRC5 protein, human
• Cancer Vaccines
• Inhibitor of Apoptosis Proteins
• Interferon-alpha
• Peptide Fragments
• Survivin
• Vaccines, Subunit

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cancer Vaccines (adverse effects, immunology)
• Female
• Humans
• Inhibitor of Apoptosis Proteins (adverse effects, chemistry, immunology)
• Interferon-alpha (therapeutic use)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Peptide Fragments (immunology)
• Prognosis
• Survivin
• T-Lymphocytes, Cytotoxic (immunology)
• Treatment Outcome
• Urologic Neoplasms (immunology, mortality, pathology, therapy)
• Vaccines, Subunit (adverse effects, immunology)