title: Identification of HLA-A*0201- and A*2402-restricted epitopes of mucin 5AC expressed in advanced pancreatic cancer.
abstract: OBJECTIVE
  Mucin 5AC (MUC5AC) was previously identified as being expressed in most pancreatic ductal adenocarcinomas. We studied the significance of MUC5AC expression for the development of pancreatic ductal adenocarcinoma and the possibility of using MUC5AC as a target for immunotherapy for pancreatic cancer.
  
  
  METHODS
  We immunohistochemicaly tested MUC5AC expression in 134 specimens. To assess the possibility of using the MUC5AC protein to develop an anticancer vaccine, we examined MUC5AC for possible peptide epitopes to elicit cytotoxic T lymphocytes (CTLs).
  
  
  RESULTS
  In immunohistochemical analysis, MUC5AC was absent from all cell types of the normal pancreas but was expressed de novo in 79% of invasive ductal adenocarcinoma. Clinicopathologically, primary tumors with lymph node metastasis had a significantly higher expression of MUC5AC. Next, we successfully established CTL clones stimulated by the MUC5AC-A02-1398 (FLNDAGACV) and MUC5AC-A24-716 (TCQPTCRSL) peptides, which have specific cytotoxicity against the corresponding HLA-A*0201- and A*2402-positive target cells pulsed with the candidate peptide. Each CTL clone also demonstrated its cytotoxic activity toward pancreatic cancer cells endogenously expressing MUC5AC.
  
  
  CONCLUSIONS
  Our results suggest that MUC5AC is a novel tumor-associated antigen that has potential application as a vaccine against pancreatic cancer.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Yamazoe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Takehiko
authors.initials: T
authors.lastname: Iwauchi
authors.forename: Mami
authors.initials: M
authors.lastname: Yoshii
authors.forename: Gentaro
authors.initials: G
authors.lastname: Ito
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Amano
authors.forename: Nobuya
authors.initials: N
authors.lastname: Yamada
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D059871:HLA-A24 Antigen / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; C438506:HLA-A*24:02 antigen; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007371:Interferon-gamma