Tumor-associated antigen and neoantigen peptides presented on Major Histocompatibility Complex (MHC) molecules (TAA/Neoantigen-MHC complex)

Tumor-associated antigens (TAAs) and neoantigens are short peptide fragments derived from intracellular proteins that are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Frontiers in Immunology, 2024). TAAs are typically overexpressed self-proteins, while neoantigens arise from somatic mutations unique to the tumor, making them highly specific targets for the immune system (NIH, 2024). These peptide-MHC (pMHC) complexes are the primary ligands for T-cell receptors (TCRs), enabling cytotoxic T-cells to identify and eliminate malignant cells (Nature, 2019). Therapeutic approaches targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, bispecific T-cell engagers (BiTEs), and personalized cancer vaccines (AACR, 2024). For example, drugs like tebentafusp target specific pMHC complexes to redirect T-cells against uveal melanoma (NIH, 2024). However, challenges such as HLA restriction, antigen loss, and potential cross-reactivity with healthy tissues remain significant hurdles in clinical development (Frontiers in Immunology, 2024).

Other names

pHLA complexPeptide-MHC complexMHC-associated peptidesMAPsTumor-specific antigensNeoepitopesTumor-specific mutant peptides

T-cell receptor (TCR) binding and MHC-restricted T-cell activation