Personalized tumor neoantigens (Neoantigens)

Personalized tumor neoantigens are unique peptides derived from non-synonymous somatic mutations within a patient's specific tumor genome (Schumacher & Schreiber, 2015, Science). These antigens are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they can be recognized by the T-cell receptor (TCR) of CD8+ and CD4+ T cells (Sahin & Türeci, 2018, Science). Because neoantigens are not expressed in healthy tissues, they are not subject to central thymic tolerance, making them highly immunogenic and ideal targets for precision immunotherapy (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Therapeutic strategies targeting these antigens include personalized mRNA or DNA vaccines, peptide vaccines, and adoptive T-cell therapies (Ott et al., 2017, Nature). By stimulating a robust, tumor-specific immune response, these treatments aim to eliminate malignant cells while sparing normal tissue. The identification of these targets typically requires high-throughput sequencing and bioinformatic algorithms to predict which mutations will result in high-affinity MHC-binding peptides (Sahin et al., 2017, Nature). Clinical development of drugs like mRNA-4157 and Autogene cevumeran has demonstrated the potential of these targets to improve outcomes in cancers such as melanoma and pancreatic cancer.

Other names

Tumor-specific neoantigensNeoepitopesPatient-specific tumor antigensSomatic mutation-derived antigensTumor-specific antigens (TSAs)

Induction of tumor-specific T-cell responses through the presentation of patient-specific mutated peptides via MHC molecules to activate CD4+ and CD8+ T cells.