HER-2/neu-derived peptide 884–899 is expressed by human breast, colorectal and pancreatic adenocarcinomas and is recognized by in-vitro-induced specific CD4⁺ T cell clones

Abstract.

HER-2/neu peptides recognized in the context of HLA-DR molecules by CD4⁺ Th lymphocytes on antigen-presenting cells have been identified. In this report, we demonstrate for the first time that HER-2/neu helper epitopes are also expressed on the surface of metastatic breast, colorectal and pancreatic carcinomas. Peripheral blood mononuclear cells from an HLA-DR4 healthy donor were used to induce HER-2/neu peptide-specific CD4⁺ T cell clones by in vitro immunization with HER-2/neu peptide (884–899)-pulsed autologous dendritic cells (DCs). Strong proliferation and significant levels of IFN-γ were induced by the CD4⁺ T cell clones in response to specific stimulation with autologous DCs loaded with HER-2(884–899). Furthermore, these clones also recognized HER-2/neu⁺ tumor cell lines, and tumor cells from breast, colorectal and pancreatic adenocarcinomas induced to express HLA-DR4, but also the HLA-DR4⁺ melanoma cell line FM3 transfected to express HER-2/neu. The recognition of tumor cells was strongly inhibited by an anti-HLA-DR mAb. Taken altogether, we provide novel information for the role of HER-2(884–899) as a naturally processed epitope expressed by breast, colorectal and pancreatic carcinomas and the capacity of HER-2/neu protein to follow the endogenous class II processing pathway. Our results suggest that HER-2(884–899) might be attractive for broadly applicable vaccines and may prove useful for adoptive immunotherapy designed for breast, colorectal and pancreatic carcinomas.