Tumor-specific mutation-derived neoantigen (Neoantigen)

Tumor-specific mutation-derived neoantigens are novel peptides arising from somatic mutations in cancer cells, such as single nucleotide variants, insertions/deletions, or gene fusions, which are processed and presented on the cell surface by major histocompatibility complex (MHC) molecules.[1][2][3][7] Absent in healthy tissues, they appear "non-self" to the immune system, triggering robust T-cell responses, particularly from cytotoxic CD8+ T cells, without central tolerance issues that limit responses to shared tumor-associated antigens.[2][3][5][7] In cancer, neoantigens enable precise tumor targeting, especially in high-mutational-burden tumors like melanoma, glioblastoma, and lung cancer, where they drive personalized immunotherapies.[1][2][4] Therapies exploit them through vaccines that prime T cells with patient-specific neoantigen sequences, adoptive T-cell transfers isolating and expanding neoantigen-reactive cells, or engineered TCR/CAR-T cells for enhanced specificity.[1][2][5] Identification involves sequencing tumor and normal DNA to predict immunogenic neoepitopes via MHC-binding algorithms.[1][5] Challenges include tumor evolution causing antigen loss, immunosuppressive microenvironments, and identification of high-quality targets amid heterogeneous mutations.[2] Neoantigen burden correlates with immunotherapy response, positioning it as a key biomarker for patient selection in checkpoint inhibitors and emerging combination regimens.[4][6] Overall, neoantigens represent a cornerstone of precision oncology, shifting treatment toward individualized immune attack on cancer cells.[2][8][9]

Other names

Tumor-specific antigen (TSA)neoepitope

Personalized neoantigen vaccines (stimulate T-cell responses via peptide or mRNA presentation); Neoantigen-targeted T-cell therapy (expand and infuse T cells with TCRs recognizing neoantigens); TCR-engineered T cells (modify T cells to express neoantigen-specific TCRs); CAR-T cells targeting neoantigens