Melanocyte protein PMEL (gp100) (gp100)

Melanocyte protein PMEL, commonly referred to as gp100, is a type I transmembrane glycoprotein primarily expressed in melanocytes and is essential for the maturation of melanosomes (UniProt P17683). It functions by forming a fibrous matrix within the melanosome that facilitates the transition from Stage I to Stage II, providing a scaffold for melanin deposition (NCBI Gene ID: 6490). In the context of oncology, gp100 is highly overexpressed in both cutaneous and uveal melanoma, making it a significant tumor-associated antigen. Specific peptide fragments, or epitopes, such as gp100:209-217 and gp100:280-288, are processed and presented by MHC Class I molecules (notably HLA-A*02:01) to CD8+ cytotoxic T cells (Rosenberg et al., Nature Medicine 1998). Therapeutic interventions targeting these epitopes include the FDA-approved bispecific T-cell engager tebentafusp, which redirects T cells to kill gp100-positive tumor cells (Nathan et al., NEJM 2021). While effective, these therapies often result in on-target off-tumor toxicities in healthy pigmented tissues, such as the skin and eyes, leading to conditions like vitiligo or uveitis.

Other names

PMEL17Silver locus protein homologME20Melanocyte-specific lineage antigen gp100Premelanosome proteinSISILV

T-cell redirection via bispecific T-cell engagers (ImmTACs) or activation of antigen-specific CD8+ T cells through peptide vaccination and TCR-engineered adoptive cell therapy.