Patient-specific tumor neoantigen peptides presented on Major Histocompatibility Complex (Neoantigen-MHC)

Patient-specific tumor neoantigen peptides presented on Major Histocompatibility Complex (MHC) are unique protein fragments derived from somatic mutations within a patient's tumor (Schumacher & Schreiber, 2015). These mutations, which include single-nucleotide variants and frameshifts, create novel amino acid sequences that are absent in healthy tissues (Sahin & Türeci, 2018). Once processed, these peptides are displayed on the cell surface by MHC molecules, where they can be recognized by the T-cell receptor (TCR) of CD8+ or CD4+ T cells (Ott et al., 2017). This recognition triggers a targeted immune response against the cancer cells while sparing normal cells, making them ideal targets for precision oncology (Blass & Ott, 2021). Current therapeutic approaches include personalized vaccines (mRNA, DNA, or peptide-based) and adoptive T-cell therapies designed to enhance the frequency and activity of neoantigen-specific T cells (Hu et al., 2021). However, the high degree of inter-patient variability necessitates a bespoke manufacturing process for each individual. Challenges include the accurate prediction of which mutations will lead to immunogenic peptides and the potential for tumor escape through the downregulation of MHC expression (Gubin et al., 2015).

Other names

Tumor-specific neoantigensNeoepitopesPersonalized neoantigensTumor-specific antigens (TSAs)MHC-restricted neoantigenspMHC complexes

Induction of a de novo T-cell response or expansion of existing neoantigen-specific T-cells that recognize and eliminate tumor cells through the release of cytotoxic granules and cytokines (Schumacher & Schreiber, 2015).