Personalized Neoantigen DNA Cancer Vaccines: Current Status and Future Perspectives

Abstract

Tumor mutation-derived neoantigens are considered promising targets for cancer immunotherapy. Personalized vaccines have emerged as an approach to deliver neoantigens and thereby trigger the induction of specific T-cell responses that can find and eliminate tumor cells based on the cell-surface presence of neoantigens. To this end, several neoantigen vaccine formats have provided encouraging results in clinical trials, resulting in neoantigen immunogenicity and clinical benefit. DNA offers a versatile and safe platform to deliver neoantigens and immune stimulants in a single entity through vaccination. Herein, we provide an overview of how DNA vaccines are being used as a means to deliver personalized neoantigens to cancer patients. We summarize the developments in DNA vaccine formulation and delivery technologies that contribute to elicit robust immune responses after vaccination. We outline the main results from central preclinical and clinical investigations, showing that neoantigen DNA vaccines induce a specific immune response directed against tumor neoantigens. Lastly, we discuss the opportunities and challenges for neoantigen DNA vaccines as an individualized approach to immunotherapy of cancer.