A Potent Immunogenic General Cancer Vaccine That Targets Survivin, an Inhibitor of Apoptosis Proteins

• Published in: Clinical cancer research 2005-02, Vol.11 (4), p.1474-1482
• Main Authors: IDENOUE, Satomi, HIROHASHI, Yoshihiko, KANASEKI, Takayuki, IKEDA, Hideyuki, KASHIWAGI, Kiyoteru, OKAZAKI, Minoru, SASAKI, Kazuaki, SATO, Takashi, OHMURA, Tousei, HATA, Fumitake, YAMAGUCHI, Koji, HIRATA, Koichi, TORIGOE, Toshihiko, SATO, Noriyuki, SATO, Yuriko, TAMURA, Yasuaki, HARIU, Hiroyuki, YAMAMOTO, Masaaki, KUROTAKI, Takehiro, TSURUMA, Tetsuhiro, ASANUMA, Hiroko
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adult; Aged; Amino Acid Sequence; Antineoplastic agents; Apoptosis - immunology; Biological and medical sciences; Breast Cancer; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Vaccines - immunology; Cell Line, Transformed; Colon Cancer; Colonic Neoplasms - immunology; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; CTL; Cytotoxicity, Immunologic - immunology; Female; Gastric Cancer; HLA-A Antigens - immunology; HLA-A24; HLA-A24 Antigen; Humans; Immunohistochemistry; Inhibitor of Apoptosis Proteins; K562 Cells; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Male; Medical sciences; Microtubule-Associated Proteins - analysis; Microtubule-Associated Proteins - immunology; Middle Aged; Neoplasm Proteins; Oligopeptides - immunology; Pharmacology. Drug treatments; Stomach Neoplasms - immunology; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0817

We reported previously a HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8 + CTL. This peptide was derived from survivin protein, an inhibitor of apoptosis proteins, expressed in a variety of tumors, such as adenocarcinoma, squamous cell carcinoma, and malignant melanoma. In this report, we provide further evidence that survivin-2B80-88 peptide might serve as a potent immunogenic cancer vaccine for various cancer patients. Overexpression of survivin was detected in surgically resected primary tumor specimens of most breast and colorectal cancers and some gastric cancers as assessed by immunohistochemical study. HLA-A24/survivin-2B80-88 tetramer analysis revealed that there existed an increased number of CTL precursors in peripheral blood mononuclear cells (PBMC) of HLA-A24 + cancer patients, and in vitro stimulation of PBMCs from six breast cancer patients with survivin-2B80-88 peptide could lead to increases of the CTL precursor frequency. Furthermore, CTLs specific for this peptide were successfully induced from PBMCs in all 7 (100%) patients with breast cancers, 6 of 7 (83%) patients with colorectal cancers, and 4 of 7 (57%) patients with gastric cancers. These data indicate that survivin expressed in tumor tissues is antigenic in cancer patients, and survivin-2B80-88-specific CTLs are present in PBMCs of various cancer patients. Our study raises the possibility that this peptide may be applicable as a general cancer vaccine to a large proportion of HLA-A24 + cancer patients.