Pancreas Carcinoma Antigen Fused to Invariant Chain Elicits T-Cell Response and Tumor Growth Inhibition

Objectives: The major histocompatibility complex class 11 chaperone invariant chain (Ii) is widely used as a carrier for inserted antigenic sequences and their introduction into the class If processing pathway. The tumor-associated antigen core 2 beta 1,6 N-acetylglucosaminyl-transferase (C2GnT), a glycosyltransferase present in human pancreatic tumor cells, is not expressed by normal pancreatic tissues. Methods: A set of expression vectors was engineered where the class 11 binding region of Ii was replaced by C2GnT-derived sequences. We investigated in vitro whether dendritic cells transfected with Ii-C2GnT constructs were capable to stimulate proliferation of CD4(+) T cells. We also tested whether vaccination with Ii-C2GnT would protect mice from tumor development. Results: Invariant chain-C2GnT fusion proteins bind to human DR1, DR3, DR4 and to mouse I-A(b) molecules. Our results demonstrate that the plasmid DNA encoding the C2GnT epitope embedded in Ii induces tumor-specific T-cell responses. Mice immunized with the Ii constructs showed reduced growth of Panc02 pancreatic tumor cells. Conclusions: Therefore, Ii clipped with the tumor-associated antigen C2GnT shows promise for the treatment of pancreatic cancer.