Neoantigen-Major Histocompatibility Complex (NeoAg-MHC) (NeoAg-MHC)

The Neoantigen-Major Histocompatibility Complex (NeoAg-MHC) is a personalized therapeutic target in oncology, formed by the presentation of mutant peptides (neoantigens) on the surface of tumor cells by MHC molecules [9, 10]. These neoantigens are derived from somatic mutations unique to an individual patient's tumor, making them highly specific markers that distinguish malignant cells from healthy tissue [2, 15]. The recognition of these complexes by the T-cell receptors (TCRs) of autologous tumor-infiltrating lymphocytes (TILs) or engineered T cells is the fundamental mechanism behind several advanced immunotherapies [1, 12]. For instance, TIL therapy involves the isolation, expansion, and re-infusion of a patient's own T cells that naturally recognize these neoantigen-MHC targets [1, 13]. Additionally, personalized neoantigen vaccines aim to prime the immune system to recognize these specific complexes [12, 15]. While this target offers high specificity and the potential for durable clinical responses, its effectiveness can be hindered by tumor-mediated immune evasion, such as MHC downregulation or the presence of an immunosuppressive microenvironment [10, 17].

Other names

Neoepitope-MHC complexTumor-specific antigen-MHC complexPatient-specific TAA-MHC complexMutant peptide-MHC complexpMHC complex

Adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TILs) or T-cell receptor (TCR)-engineered T cells that recognize and bind to the neoantigen-MHC complex on tumor cells, triggering cytotoxic T-cell activation, release of perforin and granzymes, and subsequent tumor cell apoptosis [1, 12, 14].