Neoantigen peptide–Major Histocompatibility Complex (NeoAg-MHC)

The Neoantigen peptide–Major Histocompatibility Complex (MHC) is a molecular assembly consisting of a tumor-specific mutated peptide (neoantigen) bound to an MHC Class I or Class II molecule (NIH, 2025). These complexes are displayed on the surface of cancer cells or professional antigen-presenting cells (APCs) and serve as the primary ligands for T-cell receptors (TCRs) (Kactus Bio, 2024). Recognition of the neoantigen-MHC complex by CD8+ or CD4+ T cells is a critical step in the adaptive immune response against malignancy (NIH, 2025; Frontiers in Immunology, 2024). Because neoantigens arise from somatic mutations unique to the tumor and are not subject to central tolerance, these complexes are highly specific targets for immunotherapy, minimizing off-target effects on healthy tissues (Kactus Bio, 2024; Frontiers in Immunology, 2024). Therapeutic strategies targeting these complexes include personalized neoantigen vaccines, TCR-engineered T-cell (TCR-T) therapies, and bispecific T-cell engagers (Kactus Bio, 2024; ResearchGate, 2026). However, challenges such as MHC downregulation, low neoantigen immunogenicity, and the need for complex patient-specific identification remain significant hurdles in clinical development (ResearchGate, 2025; Kactus Bio, 2024).

Other names

Neoantigen-MHC complexpMHC complexTumor-specific antigen-MHC complexHLA-neoantigen complexNeoepitope-MHC complexNeoantigen peptide–MHC class I/II complex

Therapeutic agents targeting the neoantigen-MHC complex function by either delivering synthetic neoantigen peptides or nucleic acids to facilitate the endogenous formation of these complexes on antigen-presenting cells, thereby priming neoantigen-specific T cells (vaccines), or by providing engineered T cells or antibodies that directly recognize and bind the complex on the surface of tumor cells to induce targeted cell lysis (TCR-T, bispecifics).