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

The Human leukocyte antigen A*02:01-presented gp100 peptide complex is a specific antigen-MHC target primarily utilized in the treatment of melanoma (Nathan et al., 2021, NEJM). Gp100 (also known as PMEL) is a lineage-specific glycoprotein involved in melanosome maturation and is highly overexpressed in melanoma cells compared to normal tissues (UniProt P17683). In patients with the HLA-A*02:01 allele, specific peptides derived from gp100, such as the YLEPGPVTA epitope, are processed and presented on the cell surface (FDA Kimmtrak Label). This complex serves as a highly specific target for T-cell receptor (TCR)-based therapies, which can distinguish the peptide-MHC complex from other surface proteins. The most prominent drug targeting this complex is Tebentafusp, a bispecific protein that redirects T cells to kill gp100-expressing tumor cells (Damato et al., 2019). Therapeutic engagement of this target is restricted to patients who are HLA-A*02:01 positive, making HLA typing a critical biomarker for treatment. While effective, targeting this complex can lead to immune-mediated side effects in normal melanocyte-containing tissues, such as the skin and uvea (Kimmtrak Prescribing Information).

Other names

gp100/HLA-A2 complexPMEL/HLA-A*02:01 complexgp100 peptide-MHC complexMelanocyte protein PMEL/HLA-A2gp100:209-217/HLA-A2 complex

T-cell redirection via a bispecific T-cell receptor (TCR) fusion protein that binds the peptide-MHC complex on tumor cells and CD3 on T cells, leading to T-cell activation and tumor lysis (FDA Kimmtrak Label).