Glycoprotein 100 peptide YLEPGPVTA-Human Leukocyte Antigen-A*02:01 complex (gp100:YLEPGPVTA-HLA-A*02:01)

The gp100:YLEPGPVTA-HLA-A*02:01 peptide complex is a specific molecular target presented on the surface of melanoma cells, particularly in uveal melanoma. It consists of a 9-amino acid epitope (YLEPGPVTA) derived from the melanocyte-lineage protein glycoprotein 100 (gp100/PMEL), which is processed and presented by the Human Leukocyte Antigen (HLA) allele A*02:01 (UniProt P17683; PMID: 7507892). This complex is the primary target for tebentafusp, a first-in-class bispecific T-cell engager known as an ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer). Tebentafusp utilizes a high-affinity T-cell receptor (TCR) to recognize this specific peptide-MHC complex and an anti-CD3 effector domain to recruit and activate polyclonal T-cells, leading to the targeted lysis of tumor cells (PMID: 34551229). Because gp100 is also expressed in healthy melanocytes in the skin and eye, therapeutic targeting of this complex is associated with on-target, off-tumor toxicities such as skin rash and vitiligo. Clinical use of drugs targeting this complex requires patients to be HLA-A*02:01 positive, making HLA typing a critical companion diagnostic.

Other names

gp100(280-288)-HLA-A*02:01PMEL:280-288-HLA-A*02:01gp100-HLA-A2 complexMelanocyte protein PMEL peptide-MHC complex

T-cell redirection via a bispecific fusion protein (ImmTAC) that binds the peptide-MHC complex with a high-affinity TCR domain and recruits T-cells via an anti-CD3 scFv domain.