One of the critical steps to developing curative and tumor-specific immunotherapy is the identification and selection of antigens with tumor-restricted expression in order to avoid undesirable immune responses against normal tissues. Tumor neoantigens are analogous to non-self foreign proteins, therefore bypassing central tolerance and are also exquisitely tumor-specific. Seminal studies have provided compelling evidence suggesting their immunogenicity. However, the comprehensive identification of such neoantigens has only become feasible recently using next-generation massively-parallel sequencing technologies, providing unprecedented genetic information about cancer cells. In addition, refinements in class I HLA prediction algorithms, particularly NetMHCpan, have enabled the reliable prediction of peptide binding for a broad range of class I HLA alleles. Recent studies by us and others in humans and mice have leveraged these tools to demonstrate evidence of protective immunity when targeting tumor neoantigens. We have developed pipelines that leverage WES to systematically identify personal tumor mutations with immunogenic potential, which can be incorporated as antigen targets in a multi-epitope personalized therapeutic vaccine. We are pioneering this approach in a first-in-man clinical trial in melanoma.

Citation Format: Catherine J. Wu. Fighting fire with fire: Developing a personalized neoantigen cancer vaccine. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA18.