Human leukocyte antigen A*02:01 presenting modified gp100 (209-217) peptide (HLA-A2/gp100(209-217)2M)

The Human leukocyte antigen A*02:01 presenting modified gp100 (209-217) peptide is a peptide-major histocompatibility complex (pMHC) that serves as a critical target for immunotherapy in melanoma (Source: FDA Kimmtrak Label). The gp100 protein, or PMEL, is a lineage-specific antigen involved in melanosome biogenesis and is highly expressed in melanocytes and melanoma cells (Source: UniProt P40967). The specific epitope spanning amino acids 209-217 (ITDQVPFSV) is modified by replacing threonine with methionine at position 210 (T210M) to significantly increase its binding affinity for the HLA-A*02:01 molecule (Source: Hernandez et al., 2000, J. Immunol.). This modification makes the complex a more potent target for T-cell receptor (TCR)-based interventions. Tebentafusp, a first-in-class bispecific T-cell engager (ImmTAC), specifically recognizes this pMHC complex to redirect T-cells to tumor cells (Source: Nathan et al., 2021, NEJM). This therapeutic strategy has proven particularly effective in treating metastatic uveal melanoma, a disease with historically limited treatment options. Because the target is specific to the HLA-A*02:01 allele, patient selection via HLA typing is mandatory for treatment efficacy (Source: Kimmtrak Prescribing Information). The interaction between the drug's TCR domain and the pMHC complex triggers T-cell activation and the release of inflammatory cytokines, leading to direct lysis of the target melanoma cells.

Other names

HLA-A*02:01-gp100(209-217)2Mgp100:209-217(210M) HLA-A2 complexPMEL:209-217(210M) HLA-A*02:01gp100 peptide-MHC complex

T-cell redirection via a bispecific T-cell engager (ImmTAC) that binds the peptide-MHC complex with high affinity and recruits T-cells through CD3 binding.