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

Patient-specific tumor neoantigens are unique peptides derived from non-synonymous somatic mutations, such as single nucleotide variants or frameshifts, that occur exclusively within a patient's tumor cells (Schumacher & Schreiber, 2015, Science). These mutated proteins are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I or Class II molecules (Ott et al., 2017, Nature). Because these neoantigens are not expressed in normal tissues, they are recognized as "non-self" by the immune system, allowing them to bypass central tolerance and trigger a potent T-cell response (Blass & Ott, 2021, Nature Reviews Clinical Oncology). This specificity makes the neoantigen-MHC complex an ideal target for personalized immunotherapies, including cancer vaccines and adoptive T-cell transfers (Sahin & Türeci, 2018, Science). Current clinical developments, such as mRNA-4157 and BNT122, focus on identifying these unique sequences through genomic sequencing and bioinformatic modeling to stimulate a patient's own immune system against their specific tumor (Hu et al., 2021, Nature Reviews Immunology). Despite their promise, challenges include the high degree of intratumor heterogeneity and the potential for "antigen escape," where tumors downregulate MHC expression to avoid detection (Jhunjhunwala et al., 2021, Nature Reviews Cancer).

Other names

Tumor-specific neoantigenNeoepitopeMutation-derived antigenTumor-specific antigen (TSA)Patient-specific neoantigen

Induction of a targeted immune response where T-cell receptors (TCRs) recognize and bind to the specific neoantigen-MHC complex, leading to the release of cytotoxic granules and tumor cell apoptosis (Schumacher & Schreiber, 2015, Science).