Patient-specific clonal neoantigen–MHC complex (NeoAg-MHC) (NeoAg-MHC)

Patient-specific clonal neoantigen–MHC complexes are unique molecular signatures found on the surface of malignant cells, resulting from somatic mutations that occur during tumorigenesis (Schumacher & Schreiber, 2015) [3]. These complexes consist of a mutated peptide, known as a neoantigen, bound to a patient's specific Major Histocompatibility Complex (MHC) molecule (Sahin & Türeci, 2018) [2]. Because these mutations are absent in healthy tissues, they serve as highly specific targets for the immune system, significantly reducing the risk of off-target autoimmunity compared to traditional tumor-associated antigens (McGranahan et al., 2016) [1]. Clonal neoantigens are particularly valuable therapeutic targets because they are derived from early "trunk" mutations present in all tumor cells, which helps overcome the challenge of intratumoral heterogeneity (McGranahan et al., 2016) [1]. Therapeutic interventions targeting these complexes include personalized mRNA or peptide vaccines, such as mRNA-4157, and adoptive T-cell therapies utilizing engineered T-cell receptors (TCRs) (Blass & Ott, 2021) [5]. By specifically engaging the adaptive immune system, these treatments aim to achieve precise and durable elimination of the tumor mass (Hu et al., 2021) [4].

Other names

Tumor-specific neoantigenClonal neoepitopePersonalized neoantigenPeptide-MHC (pMHC) complexTrunk neoantigenTumor-specific antigen (TSA)

Induction of de novo tumor-specific T-cell responses or expansion of existing memory T-cells that recognize mutated peptides presented by MHC molecules, leading to the targeted destruction of tumor cells by cytotoxic CD8+ T-lymphocytes (Sahin & Türeci, 2018) [2].