Melanocyte protein PMEL (gp100) epitope (gp100 epitope)

Melanocyte protein PMEL, commonly referred to as gp100, is a type I transmembrane glycoprotein primarily expressed in melanocytes and highly overexpressed in most melanoma cells (UniProt: P17683). Its biological function involves the formation of the fibrillar matrix within stage II melanosomes, which is essential for the sequestration and polymerization of melanin (PubMed: 11259604). In the context of oncology, gp100-derived epitopes are short peptide fragments (such as gp100:209-217) that are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, specifically HLA-A*02:01 (PubMed: 21670344). These epitopes serve as potent targets for various immunotherapeutic strategies, including peptide vaccines, T-cell receptor (TCR) engineered T-cells, and bispecific T-cell engagers (NCI Drug Dictionary). The most prominent drug targeting this epitope is Tebentafusp, a bispecific protein that redirects T cells to kill gp100-expressing tumor cells by binding both the gp100 peptide-HLA complex and the CD3 receptor on T cells (FDA: Kimmtrak Label). While gp100 is a valuable target due to its high expression in melanoma, its presence in normal melanocytes in the skin, eye, and inner ear can lead to on-target, off-tumor toxicities. These toxicities often manifest as vitiligo, rash, or ocular inflammation. Clinical monitoring for cytokine release syndrome is also critical during treatment with T-cell redirecting therapies targeting this epitope (FDA: Kimmtrak Label).

Other names

PMEL17Silver locus protein homologME20Melanoma-associated antigen gp100Pmel17gp100-derived peptide

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes, T-cell redirection via bispecific molecules, and active immunization using synthetic peptides.