%0 Journal Article
%T 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
%A Toshiaki Tanaka
%A Hiroshi Kitamura
%A Ryuta Inoue
%A Sachiyo Nishida
%A Akari Takahashi-Takaya
%A Sachiyo Kawami
%A Toshihiko Torigoe
%A Yoshihiko Hirohashi
%A Taiji Tsukamoto
%A Noriyuki Sato
%A Naoya Masumori
%J Journal of Immunology Research
%D 2013
%R 10.1155/2013/262967
%X We previously identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80每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汐) enhanced the effects of the vaccine for colorectal cancer. Therefore, we started a new phase I clinical trial of survivin-2B80每88 vaccination with IFN汐 for MUC patients. Twenty-one patients were enrolled and no severe adverse event was observed. HLA-A24/survivin-2B80每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汐 on the vaccination were unclear for MUC. Throughout two trials, 30 MUO patients received survivin-2B80每88 vaccination. Patients receiving the vaccination had significantly better overall survival than a comparable control group of MUO patients without vaccination . Survivin-2B80每88 vaccination may be a promising therapy for selected patients with MUC refractory to standard chemotherapy. This trial was registered with UMIN00005859. 1. Introduction Urothelial carcinoma of the bladder is the fourth most common cancer in men [1]. Systemic chemotherapy has been the mainstay of management for metastatic urothelial cancer [2, 3], and cisplatin-based combinations have evolved as the standard first-line therapy. The regimens consisting of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin (GC) are currently employed and provide prolongation of survival up to 14.8 and 13.8 months, respectively [3]. However, no standard therapy has been established for patients with progressive disease after the first-line chemotherapy [2, 3], and some new regimens including other anticancerous agents such as paclitaxel, ifosphamide, nedaplatin, and vinflunine are used in this setting [4每6], although they have not been proven to have sufficient clinical efficacy. On the other hand, during the past two decades, research on human tumor immunology and cancer immunotherapy has progressed. Immunization with peptides derived from cancer-specific antigen induces antitumor cytotoxic T lymphocytes (CTLs) [7每9]. A large number of cancer-specific antigens have been identified from melanomas and other cancers, and clinical trials of peptide-based
%U http://www.hindawi.com/journals/jir/2013/262967/