Challenges in developing personalized neoantigen cancer vaccines

The recent success of cancer immunotherapies has highlighted the benefit of harnessing the immune system for cancer treatment. Vaccines have a long history of promoting immunity to pathogens and, consequently, vaccines targeting cancer neoantigens have been championed as a tool to direct and amplify immune responses against tumours while sparing healthy tissue. In recent years, extensive preclinical research and more than one hundred clinical trials have tested different strategies of neoantigen discovery and vaccine formulations. However, despite the enthusiasm for neoantigen vaccines, proof of unequivocal efficacy has remained beyond reach for the majority of clinical trials. In this Review, we focus on the key obstacles pertaining to vaccine design and tumour environment that remain to be overcome in order to unleash the true potential of neoantigen vaccines in cancer therapy. Personalized neoantigen vaccines offer the potential to boost immune response a patient against their specific cancer antigens. Here, Katsikis, Ishii and Schliehe discuss the challenges that currently limit this therapeutic approach, including those related to neoantigen selection and adjuvants, and post-vaccine challenges such as the immunosuppressive tumour microenvironment. Moreover, they consider solutions that could help to overcome these obstacles.