Analysis of immunogenicity of different sizes of HER2/neu antigen

Abstract

One of the most important factors of cancer immunotherapeutic vaccine is to induce tumor antigen specific T cell response. Prior to considering how to induce T cell response efficiently, researchers should select tumor antigen with careful consideration because some tumor antigen show oncogenic property that may lead to safety problems. To reduce these concerns, tumor antigens are used in artificially mutated or truncated form so that oncogenic function would be eliminated. On the other hand, as the size of antigen determines T cell receptor epitope repertoire, it is important to maintain the original size as much as possible. In this study, we tested immunogenicity of four different sizes of HER2/neu antigens 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. In addition, all of four different sizes of antigen showed suppression of established tumor growth but the efficacy was depending on the size. Moreover, in human PBMC studies, the bigger antigen showed better CD4 and CD8 T cell responses than the others. These data demonstrate that if the oncogenic potential of antigen could be eliminated, the biggest form of antigen would show better therapeutic effects.