Developing neoantigen cancer vaccines: where are we now?

Abstract

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. This review examines recent advances in neoantigen cancer vaccine development, highlighting clinical progress across cancer types while discussing ongoing challenges and opportunities to enhance vaccine design, delivery, and combination immunotherapy approaches.