Human leukocyte antigen A*02:01–gp100 (154–162) peptide complex (HLA-A2/gp100(154-162))

The HLA-A*02:01–gp100 (154–162) peptide complex is a specific molecular target consisting of the Human Leukocyte Antigen (HLA) allele A*02:01 and a 9-amino acid epitope (KTWGQYWQV) derived from the gp100 (PMEL) protein (UniProt P17683). gp100 is a melanocyte-differentiation antigen that is highly expressed in most melanoma cells, making this complex a critical target for immunotherapy (Nathan et al., 2021, NEJM). The complex is presented on the surface of tumor cells, where it can be recognized by specific T-cell receptors (TCRs). Tebentafusp, a bispecific T-cell engager, was the first therapy approved to target this complex, specifically for the treatment of HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma (FDA, 2022). By binding both the HLA-peptide complex on tumor cells and the CD3 receptor on T-cells, such therapies redirect T-cell cytotoxicity toward the cancer cells (Middleton et al., 2020, Clinical Cancer Research). Therapeutic challenges include on-target, off-tumor effects, as gp100 is also expressed in healthy melanocytes in the skin and eye, leading to common side effects like rash and pruritus (Hassel et al., 2023, Cancer Treatment Reviews). This target represents a significant advancement in TCR-based therapeutics, moving beyond traditional monoclonal antibodies to target intracellular proteins presented via MHC.

Other names

HLA-A*02:01-PMEL(154-162)HLA-A2-gp100:154-162gp100:154-162/HLA-A*02:01KTWGQYWQV-HLA-A*02:01 complex

T-cell redirection via a bispecific fusion protein consisting of a high-affinity T-cell receptor (TCR) fused to an anti-CD3 effector domain (ImmTAC).