Patient-specific tumor neoantigen peptide-MHC complex (NeoAg-MHC)

Patient-specific tumor neoantigen peptides presented on MHC class I and II molecules are unique fragments of proteins resulting from somatic mutations within a patient's tumor cells (Schumacher & Schreiber, 2015). These neoantigens are processed by the cellular machinery and displayed on the cell surface, where they serve as non-self signals to the immune system, specifically recognized by T-cell receptors (TCRs) on CD8+ and CD4+ T cells (Sahin & Türeci, 2018). Because these antigens are absent from the normal human genome, they are highly attractive therapeutic targets as they minimize the risk of autoimmune cross-reactivity and bypass central tolerance (Hu et al., 2021). Therapeutic interventions targeting these complexes primarily involve personalized cancer vaccines—utilizing mRNA, DNA, or peptides—and adoptive cell transfer of TCR-engineered T cells (Ott et al., 2017). These therapies aim to stimulate or provide a robust, tumor-specific immune response capable of infiltrating the tumor microenvironment and eliminating malignant cells. Despite their promise, the clinical application of neoantigen-targeted therapies faces challenges such as the high cost and time required for individualized manufacturing, the potential for tumor escape through the loss of HLA expression, and the difficulty in accurately predicting which mutations will result in truly immunogenic peptides (Hu et al., 2021).

Other names

Tumor-specific antigensNeoepitopesMutation-derived antigensTSAspMHC complexesNeoantigens

Vaccine-mediated induction of de novo neoantigen-specific T-cell responses or direct targeting via TCR-engineered T-cells to induce tumor cell lysis (Sahin & Türeci, 2018).