Patient-specific tumor-associated antigens (Neoantigens) (Neoantigens)

Patient-specific tumor-associated antigens, primarily known as neoantigens, are unique peptides derived from non-synonymous somatic mutations, insertions, deletions, or gene fusions specific to an individual's tumor (Schumacher & Schreiber, 2015, Science). These antigens are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) class I and class II molecules, where they serve as targets for CD8+ cytotoxic T cells and CD4+ helper T cells, respectively (Alspach et al., 2019, Nature). Because neoantigens are absent from the normal human proteome, they are highly immunogenic and bypass central thymic tolerance, making them ideal candidates for precision immunotherapy (Sahin & Türeci, 2018, Science). Current therapeutic approaches include personalized mRNA or peptide-based vaccines designed to elicit a de novo immune response, as well as adoptive cell therapies like tumor-infiltrating lymphocytes (TILs) that are naturally primed against these antigens (Ott et al., 2017, Nature). Patient selection for these therapies often relies on biomarkers such as tumor mutational burden and HLA typing to ensure the presence of targetable mutations and the capability of the patient's immune system to present them (Hu et al., 2021, Nature Reviews Immunology). While targeting these antigens offers high specificity, challenges include the high degree of intratumoral heterogeneity and the potential for tumors to evade the immune system by downregulating MHC expression or through the loss of the target mutation (Garrido et al., 2016, Cancer Immunology, Immunotherapy).

Other names

NeoantigensTumor-specific antigensTSAsPatient-specific TAAspMHC complexesTumor-specific neoantigensMutation-derived antigens

Induction of a polyclonal T-cell response targeting unique tumor-specific mutations presented on MHC molecules to elicit tumor cell lysis.