Kinase domain deleted engineered HER2 could elicit efficient tumor immune response

Abstract In tumor immunotherapeutic vaccines, it is important to select tumor-associated antigen because of immunogenicity and oncogenic properties of tumor antigens. Many vaccination platforms were developed to enhance immunogenicity of antigens. In addition, many strategies are using tumor antigens in artificially mutated or truncated forms to eliminate oncogenic function of antigens. On the other hand, as the T cell immune responses depend on the recognition of epitopes that are loaded on the MHC class I molecules, it is important to maintain the original size as much as possible. In this study, we engineered HER2 antigens with four different forms, K684, K965, K1001, and K1117 and tested immunogenicity in B cell and monocyte based vaccine models. In murine models, we observed antigen specific T cell response in the antigen size dependent manner and antigen specific antibody response in the antigen expression dependent manner. We also tested tumor therapeutic models with full-length HER2 expressing CT26. All of four antigens showed tumor suppression in full-length HER2 expressing CT26 tumor models and K1117 showed highest therapeutic effect. In addition, the K1117 showed significant therapeutic effect in HER2 intracellular domain expressing CT26 tumor models compared to the K684. Moreover, in human PBMC studies, the K1117 showed better CD4 and CD8 T cell responses than the others did. These data suggested that antigens containing wide epitope repertoire could show better therapeutic effect.