Tumor-specific neoantigen-major histocompatibility complex (NeoAg-MHC)

Tumor-specific neoantigen-major histocompatibility complexes (NeoAg-MHC) represent a class of highly specific therapeutic targets formed when mutated proteins unique to a patient's tumor are processed and presented on the cell surface by MHC molecules. Unlike shared tumor-associated antigens, these neoantigens arise from somatic mutations (such as SNVs or indels) and are absent from healthy tissues, significantly reducing the risk of central tolerance and autoimmune cross-reactivity (Nature, 2017, 547:217-221). These complexes are recognized by the T-cell receptors (TCRs) of CD8+ and CD4+ T cells, triggering a targeted immune response against the malignancy (Science, 2015, 348:124-128). Therapeutic strategies targeting these complexes include personalized mRNA or DNA vaccines designed to prime the immune system, and adoptive cell therapies such as TCR-engineered T cells (TCR-T) that directly bind the pMHC (NEJM, 2022, 386:2112-2119). Because neoantigens are unique to each patient, they are the cornerstone of precision oncology and personalized immunotherapy, though their efficacy can be limited by tumor heterogeneity and mechanisms of immune escape like HLA loss (Nature Reviews Cancer, 2021, 21:283-300).

Other names

Patient-specific tumor-associated antigenNeoantigen-peptide-MHC complexpMHC complexTumor-specific antigen (TSA)Neoepitope-HLA complex

T-cell receptor (TCR) binding and activation, induction of cytotoxic T-lymphocyte (CTL) response, and immune-mediated tumor cell lysis.