Human dendritic cells transfected with amplified MUC1 mRNA stimulate cytotoxic T lymphocyte responses against pancreatic cancer in vitro

Abstract Background and Aim: Mucin (MUC) 1 is an epithelial cell glycoprotein that is aberrantly overexpressed in many adenocarcinomas, including pancreatic cancer (PC), providing an ideal tumor‐associated antigen and target for immunotherapy. In this study, we investigated whether the cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) transfected with amplified MUC1 mRNA could respond against PC in vitro . Methods: Amplified mRNA encoding MUC1 were transfected into DCs using electroporation with an optimized setting and the MUC1 expression were evaluated by quantitative real‐time polymerase chain reaction and Western blot. The MUC1 specific CTL responses were measured using the standard chromium 51 (51Cr)‐release assays and the interferon‐γ release assay. Results: Dendritic cells could be transfected with amplified MUC1 mRNA efficiently. The transfected DCs were remarkably effective in stimulating MUC1‐specific CTL responses in vitro . The function of MUC1 specific CTLs, induced by MUC1 mRNA‐transfected DCs, was restricted by major histocompatibility complex (MHC) class I antigen presentation. Conclusion: The CTL responses stimulated by DCs transfected with MUC1 mRNA could only recognize and lyse HLA‐A2+/MUC1+ PC and other target cells under restriction by MHC class I‐specific antigen presentation, providing a preclinical rationale for using MUC1 as a target structure for immunotherapeutic strategies against PC.