Description

Developing and Improving Personalized Neoantigen-Targeting Cancer Vaccines

Catherine J. Wu, MD

Dana-Farber Cancer Institute and Harvard Medical School; Boston, MA, USA; Broad Institute, Cambridge, MA, USA

At the heart of any cancer and host immune cell response is the tumor antigen and host antigen-specific T cell interaction. The cytotoxic T cell-cognate antigen interaction forms the mechanistic basis for immune-mediated recognition and the killing of malignant cells. While the search for immunogenic tumor antigens has been the subject of decades-long studies, multiple lines of evidence have convincingly demonstrated tumor neoantigens as an important class of immunogenic tumor antigens. Neoantigens arise from amino acid changes encoded by somatic mutations in the tumor cell and have the potential to bind to and be presented by personal HLA molecules. Using next-generation sequencing approaches, we can now systematically identify mutations leading to amino acid changes that can be potentially recognized immunologically through the implementation of neoantigen discovery pipelines. In recent studies, we have tested the feasibility and immunogenicity of a vaccine that targets up to 20 personal neoantigens predicted to be presented by autologous patient tumor. This approach can expand the repertoire of neoantigen specific T cells, providing strong rationale for the further development of this approach, alone and in combination with checkpoint therapies.