Cancer peptide vaccine therapy developed from oncoantigens identified through genome-wide expression profile analysis for bladder cancer.
OBJECTIVE
The field of cancer vaccine therapy is currently expected to become the fourth option in the treatment of cancer after surgery, chemotherapy and radiation therapy. We developed a novel cancer peptide vaccine therapy for bladder cancer through a genome-wide expression profile analysis.


METHODS
Among a number of oncoproteins that are transactivated in cancer cells, we focused on M phase phosphoprotein 1 and DEP domain containing 1, both of which are cancer-testis antigens playing critical roles in the growth of bladder cancer cells, as candidate molecules for the development of drugs for bladder cancer. In an attempt to identify the peptide epitope from these oncoantigens, we conducted a clinical trial using these peptides for patients with advanced bladder cancer.


RESULTS
We identified HLA-A24-restricted peptide epitopes corresponding to parts of M phase phosphoprotein 1 and DEP domain containing 1 proteins, which could induce peptide-specific cytotoxic T lymphocytes. Using these peptides, we found that M phase phosphoprotein 1- and DEP domain containing 1-derived peptide vaccines could be well tolerated without any serious adverse events, and effectively induced peptide-specific cytotoxic T lymphocytes in vivo.


CONCLUSIONS
The novel approach adopted in the treatment with peptide vaccines is considered to be a promising therapy for bladder cancer.
Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan. watao@iwate-med.ac.jp
Wataru
W
Obara
Ryuji
R
Ohsawa
Mitsugu
M
Kanehira
Ryo
R
Takata
Takuya
T
Tsunoda
Koji
K
Yoshida
Kazuyoshi
K
Takeda
Toyomasa
T
Katagiri
Yusuke
Y
Nakamura
Tomoaki
T
Fujioka
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D018076:DNA, Complementary / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis; D003713:Dendritic Cells; D004334:Drug Administration Schedule; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D010455:Peptides; D040081:Protein Array Analysis; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000601:surgery
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C574714:DEPDC1-294 peptide; D018076:DNA, Complementary; D004273:DNA, Neoplasm; C574713:MPHOSPH1-278 peptide; D010455:Peptides; D005620:Freund's Adjuvant; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; C438388:KIF20B protein, human; D016547:Kinesins