RNA vaccines for cancer: Principles to practice

Vaccines are the most impactful medicines to improve health. Though potent against pathogens, vaccines for cancer remain an unfulfilled promise. However, recent advances in RNA technology coupled with scientific and clinical breakthroughs have spurred rapid discovery and potent delivery of tumor antigens at speed and scale, transforming cancer vaccines into a tantalizing prospect. Yet, despite being at a pivotal juncture, with several randomized clinical trials maturing in upcoming years, several critical questions remain: which antigens, tumors, platforms, and hosts can trigger potent immunity with clinical impact? Here, we address these questions with a principled framework of cancer vaccination from antigen detection to delivery. With this framework, we outline features of emergent RNA technology that enable rapid, robust, real-time vaccination with somatic mutation-derived neoantigens—an emerging "ideal" antigen class—and highlight latent features that have sparked the belief that RNA could realize the enduring vision for vaccines against cancer.