Neoantigens

Neoantigens are peptides derived from somatic mutations in cancer cells that are presented on MHC molecules and recognized by T cells. Unlike normal self-antigens, neoantigens are not present in healthy tissues, making them attractive targets for cancer immunotherapy.

They arise from various mutation types, including missense mutations, frameshifts and indels, gene fusions, alternative splicing, and RNA editing. For a neoantigen to be relevant, the mutant peptide must be processed by the antigen presentation pathway and bind to an individual’s HLA molecules, with adequate expression to be visible to the immune system.

Identification typically combines tumor DNA and RNA sequencing with computational prediction of MHC binding and T cell recognition. Candidate neoantigens are then validated experimentally for immunogenicity, a step increasingly incorporated into personalized cancer vaccine programs and adoptive T cell therapies.

Clinical observations link higher neoantigen burden with improved responses to immune checkpoint inhibitors, though not universally. Challenges include tumor heterogeneity, clonal versus subclonal status, limited expression, immune tolerance, and the time and cost required to generate patient-specific neoantigens.

Neoantigen research aims to develop broadly applicable cancer vaccines and targeted T cell therapies while informing prognosis and treatment choice. It remains a rapidly evolving, highly personalized area within cancer immunotherapy.