Nune Markosyan, Robert H Vonderheide
The success of immunotherapies such as immune checkpoint blockade and engineered T-cells has demonstrated the immune system's anticancer potential. Although prophylactic vaccines against oncogenic viruses such as human papillomavirus prevent cancer by blocking infection, therapeutic vaccines targeting tumour-associated or tumour-specific antigens (TAAs/TSAs) have not reliably produced meaningful tumour regressions. Advances in DNA sequencing and computational pipelines for predicting individual, MHC-restricted neoantigens now enable personalized cancer vaccines (PCVs). By targeting neoantigens arising from somatic mutations, PCVs escape the central tolerance that limits anti-TAA vaccines. Multiple clinical trials have shown promise, but PCV design, delivery, and optimal disease settings require further refinement.