Patient-specific tumor neoantigen peptides presented on MHC class I and II (NeoAg-MHC)

Patient-specific tumor neoantigen peptides presented on MHC class I and II represent a class of highly specific cancer targets derived from somatic mutations unique to an individual's tumor. These mutations, which include single nucleotide variants (SNVs), insertions/deletions (indels), and gene fusions, result in novel protein sequences that are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Xie et al., 2023, Signal Transduction and Targeted Therapy). Because these neoantigens are entirely absent from the normal human genome and healthy tissues, they are recognized by the immune system as "non-self," making them ideal targets for precision immunotherapy with a low risk of central tolerance or autoimmune toxicity (NCI Dictionary of Cancer Terms). Therapeutic strategies targeting these complexes involve the use of personalized vaccines (mRNA, DNA, or peptide-based) and adoptive T-cell therapies, such as TCR-engineered T cells (TCR-T), which are designed to recognize the specific peptide-MHC interface. The clinical efficacy of targeting these neoantigens depends on the accurate identification of mutations through whole-exome sequencing and the bioinformatic prediction of which peptides will bind most effectively to the patient's specific HLA alleles (Blass & Ott, 2021, Nature Reviews Clinical Oncology). This approach is currently a cornerstone of the next generation of individualized cancer immunotherapy, particularly in tumors with high mutational burdens.

Other names

Tumor-specific neoantigens (TSAs)NeoepitopesMHC-restricted neoantigensPersonalized tumor antigensSomatic mutation-derived antigens

Personalized therapies targeting these complexes, such as mRNA or peptide vaccines, work by introducing the neoantigen sequences into the patient to prime and expand neoantigen-specific CD8+ cytotoxic T cells (via MHC Class I) and CD4+ helper T cells (via MHC Class II). These activated T cells then recognize the specific peptide-MHC complexes displayed on the surface of tumor cells, leading to targeted cell lysis and the induction of a durable anti-tumor immune response (Sahin & Türeci, 2018, Science; Blass & Ott, 2021, Nature Reviews Clinical Oncology).