Abstract IA25: Targeting tumor neoantigens to drive effective tumor immunity

Abstract

With the recent availability of novel immunologic agents, priority has shifted to understanding the mechanisms of and predicting responses to each treatment. At the heart of cancer and host immune cell interactions is the tumor antigen and host antigen-specific T cell interaction, with the cytotoxic T cell-cognate antigen interaction forming 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 demonstrated that neoantigens can be safely and feasibly targeted to generate customized cancer vaccines. We have been undertaking pilot clinical trials to develop personal cancer vaccines in melanoma and glioblastoma that utilize synthetic long peptides as delivery approach for this therapy. Recent results and new directions will be discussed. Citation Format: Catherine J. Wu. Targeting tumor neoantigens to drive effective tumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA25.