title: High expression of MAGE-A4 and MHC class I antigens in tumor cells and induction of MAGE-A4 immune responses are prognostic markers of CHP-MAGE-A4 cancer vaccine.
abstract: OBJECTIVE
  We conducted a cancer vaccine clinical trial with MAGE-A4 protein. Safety, clinical response, and antigen-specific immune responses were analyzed and the prognostic factors by vaccination were investigated.
  
  
  METHODS
  Twenty patients with advanced esophageal, stomach or lung cancer were administered MAGE-A4 vaccine containing 300μg protein subcutaneously once every 2 weeks in six doses. Primary endpoints of this study were safety and MAGE-A4 immune responses.
  
  
  RESULTS
  The vaccine was well tolerated. Fifteen of 20 patients completed one cycle of vaccination and two patients showed SD. A MAGE-A4-specific humoral immune response was observed in four patients who had high expression of MAGE-A4 and MHC class I on tumor cells. These four patients showed significantly longer overall survival than patients without an antibody response after vaccination (p=0.009). Patients with tumor cells expressing high MAGE-A4 or MHC class I antigen showed significantly longer overall survival than those with low expression. Induction of CD4 and CD8T cell responses was observed in three and six patients, respectively, and patients with induction of MAGE-A4-specific IFNγ-producing CD8T cells, but not CD4T cells, lived longer than those without induction.
  
  
  CONCLUSIONS
  The CHP-MAGE-A4 vaccine was safe. Expression of MAGE-A4 and MHC class I in tumor tissue and the induction of a MAGE-A4-specific immune response after vaccination would be feasible prognostic markers for patients vaccinated with MAGE-A4.
authors.affiliation: Department of Gastroenterological Surgery, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Gastroenterological Surgery, Japan; Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Japan. Electronic address: hwada@gesurg.med.osaka-u.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Gastroenterological Surgery, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Gastroenterological Surgery, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Experimental Immunology, Immunology Frontier Research Center Osaka University, Suita, Osaka, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Department of Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.affiliation: Departments of Immuno-Gene Therapy and Cancer Vaccine, Mie University, Tsu, Mie, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kageyama
authors.affiliation: Departments of Immuno-Gene Therapy and Cancer Vaccine, Mie University, Tsu, Mie, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.affiliation: Department of Gastroenterological Surgery, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterological Surgery, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000628:therapy; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D008175:Lung Neoplasms / Q000628:therapy; D053758:Nanoparticles / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D013274:Stomach Neoplasms / Q000628:therapy; D015996:Survival Rate
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; C573415:IFNG protein, human; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma
keywords: CT antigen; Cancer vaccine; MAGE-A4; MHC; Monitoring; Prognosis