Tumor-associated neoantigen (TAN) (TAN)

Tumor-associated neoantigens (TANs) are unique, non-self peptides derived from somatic mutations within a tumor's genome that are not expressed in normal tissues. These peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I and class II molecules, serving as the primary targets for T-cell receptor (TCR) recognition [1]. Because they are absent from the healthy proteome, TANs are highly immunogenic and represent ideal targets for precision immunotherapy, minimizing the risk of central tolerance and off-target autoimmune toxicity [2]. Therapeutic interventions targeting these complexes include personalized neoantigen vaccines (mRNA, DNA, or peptide-based) and adoptive cell therapies, such as TCR-engineered T cells (TCR-T) [3]. These strategies aim to stimulate or provide a robust population of CD8+ cytotoxic T cells and CD4+ helper T cells specifically directed against the tumor [1]. Despite their potential, the high degree of patient-specific variation requires complex bioinformatic pipelines for neoantigen prediction and individualized manufacturing processes [2]. Furthermore, tumor evolution can lead to the loss of neoantigen expression or MHC downregulation, posing significant challenges to long-term therapeutic efficacy [3]. Sources: [1] Schumacher, T. N., & Schreiber, R. D. (2015). Neoantigens in cancer immunotherapy. Science. https://doi.org/10.1126/science.aaa4971 [2] Blass, E., & Ott, P. A. (2021). Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nature Reviews Clinical Oncology. https://doi.org/10.1038/s41571-020-00460-2 [3] Xie, N., et al. (2023). Neoantigens: promising targets for cancer therapy. Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-023-01303-8

Other names

NeoantigenTumor-specific antigen (TSA)Mutation-derived antigenNeoepitopeTumor-specific neoantigen

Activation of the adaptive immune system through the presentation of tumor-specific mutated peptides on MHC molecules, which are then recognized by T-cell receptors to trigger a targeted cytotoxic response against cancer cells [1][3].