Melanocyte protein PMEL (PMEL) (PMEL)

Melanocyte protein PMEL, also known as gp100 or PMEL17, is a type I transmembrane glycoprotein primarily expressed in the melanosomes of melanocytes in the skin and eye [2, 12, 14]. It plays a critical role in the biogenesis and maturation of melanosomes, where it forms functional amyloid fibrils that act as a structural scaffold for melanin polymerization [6, 10, 16]. In the context of oncology, PMEL is a prominent tumor-associated antigen highly expressed in both cutaneous and uveal melanoma, making it a valuable target for immunotherapy [1, 5, 18]. The most notable therapeutic intervention targeting PMEL is tebentafusp, a first-in-class bispecific T-cell engager (ImmTAC) approved for HLA-A*02:01-positive metastatic uveal melanoma [4, 8]. Tebentafusp works by redirecting cytotoxic T cells to recognize gp100-derived peptides presented on the surface of tumor cells via the HLA complex [1, 4]. Other developmental strategies include peptide vaccines and antibody-drug conjugates (ADCs) designed to exploit its lineage-restricted expression [11, 13, 19]. Clinical challenges associated with targeting PMEL include managing cytokine release syndrome and on-target toxicities affecting normal pigmented tissues, such as the skin and uvea [8, 11, 21].

Other names

Premelanosome proteinSilver locus protein homologGlycoprotein 100gp100PMEL17SILVMelanoma-associated ME20 antigenME20-MP1 proteinp100p26

Tebentafusp is a bispecific fusion protein (ImmTAC) that binds with high affinity to a gp100-derived peptide presented by HLA-A*02:01 on the surface of melanoma cells and to the CD3 receptor on T cells, thereby redirecting T cells to form an immune synapse and kill the tumor cells [1, 4, 8].