Personal Neoantigen Vaccines for the Treatment of Cancer

Abstract

Cancer vaccines can generate and amplify tumor-specific T cell responses with the promise to provide long-term control of cancer. All cancer cells harbor genetic alterations encoding neoantigens that are specific to the tumor and not present in normal tissue. Similar to foreign antigens targeted by T cells in infectious disease settings, neoantigens represent the long elusive immunogens for cancer vaccination. Since the vast majority of mutations are unique to individual tumors, neoantigen vaccines require custom design for each patient. The availability of rapid and cost-effective genome sequencing, along with advanced bioinformatics tools, now allows neoantigen-target discovery and vaccine manufacturing in sufficient time for the treatment of cancer patients. Clinical trials in melanoma and glioblastoma have demonstrated the feasibility, immunogenicity, and signals of efficacy of this personalized immunotherapy approach. Key unresolved areas include identification of the most effective vaccine delivery platforms, validation and consensus of neoantigen target selection, and optimal strategies for partnering immunotherapies. Given the universal presence of mutations in cancer and the patient-tailored paradigm, personalized neoantigen vaccines have potential applicability for all cancer patients.