Patient-specific tumor-specific neoantigen peptides presented on MHC (Neoantigen-MHC complex)

Patient-specific tumor-specific neoantigen peptides presented on the Major Histocompatibility Complex (MHC) are highly specific targets for cancer immunotherapy, arising from somatic mutations unique to an individual's tumor [Schumacher & Schreiber, 2015, Science]. These mutations, such as single-nucleotide variants or frameshifts, create novel protein sequences that are absent from the normal human proteome, allowing the immune system to distinguish malignant cells from healthy tissue [Ott et al., 2017, NEJM]. Once processed and displayed on the cell surface by MHC Class I or Class II molecules, these neoepitopes can be recognized by T-cell receptors (TCRs), triggering a robust cytotoxic or helper T-cell response [Sahin et al., 2017, Nature]. Because they are not subject to central thymic tolerance, neoantigens are often highly immunogenic and represent the primary targets of successful checkpoint inhibitor therapy and personalized vaccines [Blass & Ott, 2021, Nature Reviews Clinical Oncology]. Current therapeutic strategies involve the use of personalized mRNA, DNA, or peptide vaccines designed to prime the patient's immune system against these specific sequences [Hu et al., 2021, Nature Reviews Cancer]. Additionally, adoptive cell therapies utilize TCR-engineered T cells specifically redirected to recognize the neoantigen-MHC complex on the tumor surface [Yadav et al., 2014, Nature]. Despite their potential, challenges remain in accurately predicting which mutations will produce immunogenic peptides and overcoming tumor-mediated mechanisms of immune evasion, such as the loss of MHC expression [Gubin et al., 2015, Journal of Clinical Investigation].

Other names

Tumor neoepitopesPersonalized neoantigensMutation-derived antigensTumor-specific antigensTSAsNeoantigens

Induction of de novo T-cell responses or expansion of existing neoantigen-specific T cells to mediate tumor cell lysis [Sahin et al., 2017, Nature].