Identification of HLA-A*0201- and A*2402-Restricted Epitopes of Mucin 5AC Expressed in Advanced Pancreatic Cancer

Abstract

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. 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). 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. Our results suggest that MUC5AC is a novel tumor-associated antigen that has potential application as a vaccine against pancreatic cancer.