Abstract 4748: Identification of HLA-A*0201 and A*2402-restricted epitope peptides derived from mucin 5AC (MUC5AC) gene expressed in human pancreatic cancer as a potential target for immunotherapy

Abstract

Abstract MUC5AC was previously identified to be de novo expressed in the majority of pancreatic ductal adenocarcinoma. For the development of pancreatic cancer immunotherapy, we studied the significance of MUC5AC expressed in pancreatic ductal adenocarcinoma and the capability of MUC5AC as a target for immunotherapy of pancreatic cancer. By immunohistochemical analysis of 102 specimens, MUC5AC is absent from all cell types of the normal pancreas, but arise de novo in 85% of invasive ductal adenocarcinoma. Clinicopathlogically, tumors with lymph node metastasis had significantly higher expression of MUC5AC than those without node metastasis. To validate the potentiality of cancer vaccine, we have searched for possible epitope peptides that can elicit cytotoxic T lymphocytes (CTL) to MUC5AC. We screened 20 candidate peptides derived from MUC5AC gene sequence for each of human leukocyte antigen (HLA) - A*0201 and A*2402. As a result, we successfully established CTL clones stimulated by MUC5AC-A02-1398 (FLNDAGACV) and MUC5AC-A24-716 (TCQPTCRSL) peptide that have specific cytotoxic activities against each of the HLA-A*0201 and A*2402-positive target cells pulsed with the candidate peptide. Subsequent analysis of each CTL clones also revealed their cytotoxic activities against pancreatic cancer cells expressing MUC5AC. A cold target inhibition assay further confirmed that each CTL clones specifically recognized the major histocompatibility complex (MHC) class I-peptide complex. Our results suggested that MUC5AC is a novel tumor-associated antigen recognized by CTL, and MUC5AC-A02-1398 (FLNDAGACV) and MUC5AC-A24-716 (TCQPTCRSL) are HLA-A*0201 and A*2402-restricted epitope peptides that can induce potent and specific immune responses against pancreatic cancer cells expressing MUC5AC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4748.