Tumor neoantigen–MHC complex (pMHC)

Tumor neoantigen–MHC complexes are molecular assemblies consisting of a tumor-specific mutant peptide (neoantigen) bound to a Major Histocompatibility Complex (MHC) molecule (Source 1.2.2). These complexes are essential for the adaptive immune system's ability to recognize and eliminate cancer cells, as they provide the 'non-self' signal required for T cell activation (Source 1.5.1). On professional antigen-presenting cells (APCs), such as dendritic cells, these complexes are presented to naive T cells to initiate a systemic immune response, a process known as priming (Source 1.3.4). On the surface of tumor cells, the same complexes serve as the recognition site for cytotoxic CD8+ T cells, which induce apoptosis upon binding via their T cell receptors (TCRs) (Source 1.4.1). Therapeutic strategies targeting these complexes include personalized cancer vaccines, which aim to boost the frequency of neoantigen-specific T cells, and adoptive cell therapies using engineered T-cell receptors (TCRs) (Source 1.2.3). Additionally, TCR-mimic antibodies and bispecific T-cell engagers are being developed to target these complexes directly on the tumor cell surface (Source 1.3.1). However, the clinical efficacy of these approaches can be limited by tumor-mediated immune evasion mechanisms, such as the downregulation of MHC expression or the loss of specific HLA alleles (Source 1.2.1). The high degree of patient-specific heterogeneity in neoantigen sequences necessitates personalized therapeutic approaches, which presents significant manufacturing and regulatory challenges (Source 1.2.3).

Other names

Neoantigen-HLA complexMutant peptide-MHC complexTumor-specific antigen-MHC complexpMHC complexTumor neoantigen–MHC complexes on antigen-presenting cells

Induction of neoantigen-specific T cell immunity through vaccination; direct targeting of peptide-MHC complexes via engineered T-cell receptors (TCR-T) or TCR-mimic antibodies to induce tumor cell lysis.