HLA-A2-restricted tumor-associated antigen peptide complex (HLA-A2/TAA pMHC)

The HLA-A2-restricted tumor-associated antigen peptide complex is a molecular assembly consisting of a Human Leukocyte Antigen (HLA) class I molecule (specifically the A2 serotype) and a short peptide fragment derived from an intracellular tumor-associated antigen (TAA) [1.1.3, 1.5.1]. This complex is presented on the cell surface of malignant cells, serving as a critical recognition element for the cellular immune system [1.1.3, 1.5.1]. T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes naturally interact with these complexes to initiate an immune response [1.3.1, 1.3.5]. In oncology, this complex is a major therapeutic target for engineered T-cell receptor (TCR-T) therapies, bispecific T-cell engagers (such as ImmTACs), and cancer vaccines [1.2.2, 1.3.3, 1.5.4]. By targeting these specific peptide-MHC (pMHC) combinations, therapies can achieve high specificity for cancer cells while sparing healthy tissues that do not present the same antigen-HLA combination [1.3.5, 1.4.3]. However, challenges include the requirement for patients to be HLA-A2 positive and the risk of off-target toxicities if the peptide is also presented on normal cells [1.3.5, 1.4.4]. Notable examples of drugs targeting these complexes include Tebentafusp for uveal melanoma and Afamitresgene autoleucel for synovial sarcoma [1.2.2, 1.3.1]. These therapies work by either redirecting existing T cells or providing engineered T cells that can recognize the pMHC with high affinity [1.3.3, 1.4.4]. Safety monitoring is essential due to the potential for cytokine release syndrome and cross-reactivity with similar peptides in healthy tissues [1.2.3, 1.4.3]. Overall, this target class represents a significant advancement in precision immunotherapy for solid tumors [1.2.5].

Other names

HLA-A*02:01/peptide complexMHC-peptide complexpMHCHLA-A2-restricted epitopeTumor-specific MHC-peptide complexHLA-A2-restricted tumor antigen epitope

T-cell redirection, Adoptive T-cell transfer, T-cell activation, Cytotoxicity