Patient-specific tumor neoantigen peptides presented by MHC class I and II (Neoantigen)

Patient-specific tumor neoantigens are novel peptides derived from somatic mutations unique to an individual's tumor, such as single nucleotide variants or frameshifts [1]. These peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I and class II molecules, where they can be recognized by the host's immune system [2]. Because these antigens are not expressed in healthy tissues, they bypass central tolerance, making them highly potent targets for immunotherapy with a low risk of systemic autoimmunity [3]. Therapeutic approaches involve identifying these mutations via next-generation sequencing and delivering them as personalized vaccines (mRNA, DNA, or peptide-based) or using them to engineer T-cell receptor (TCR) therapies [4]. By specifically activating CD8+ cytotoxic T-cells and CD4+ helper T-cells against these neoepitopes, the treatment promotes a targeted and durable anti-tumor immune response [5]. Sources: [1] Schumacher & Schreiber (2015) Science; [2] Sahin & Türeci (2018) Science; [3] Blass & Ott (2021) Nat Rev Clin Oncol; [4] Xie et al. (2023) Front Immunol; [5] Lang et al. (2022) Cancer Cell.

Other names

NeoepitopeTumor-specific antigenTSAMutation-derived antigenPersonalized neoantigen

Induction of de novo T-cell responses against tumor-specific mutations through vaccination or adoptive transfer of TCR-engineered T-cells [2, 3].