Premelanosome protein (gp100) and Tyrosinase (gp100 / TYR)

Premelanosome protein (gp100) and Tyrosinase are two key melanocyte differentiation antigens (MDAs) that are frequently co-targeted in the treatment of melanoma [1, 20]. gp100 is a transmembrane glycoprotein involved in the formation of the internal matrix of melanosomes, while Tyrosinase is the rate-limiting enzyme in the melanin synthesis pathway [19, 22]. Both proteins are highly expressed in melanocytes and the majority of melanoma cells, making them ideal targets for T-cell-mediated immunotherapies, including peptide, DNA, and mRNA vaccines, as well as adoptive cell transfers [3, 7]. Tebentafusp, a bispecific T-cell engager, specifically targets a gp100 peptide presented by HLA-A*02:01 and has shown significant efficacy in uveal melanoma [7, 15]. Tyrosinase-based vaccines are often used in combination with gp100 to broaden the immune response and prevent tumor escape [8, 12]. Because these antigens are also present in normal melanocytes, therapeutic intervention can lead to autoimmune-like toxicities, most notably vitiligo and uveitis [18, 20]. Monitoring for these side effects and the expression of the antigens in tumor tissue is essential for patient management [13, 15]. Overall, these antigens remain central to the development of precision immunotherapies for both cutaneous and uveal melanoma [6, 17].

Other names

Melanoma-associated antigen gp100PMELPmel17SILVME20HMB-45 antigenMelanocyte lineage-specific antigen gp100TYROCA1SK21LB24-ABMonophenol monooxygenase

Bispecific T-cell engagement, active immunization (vaccination), and adoptive T-cell receptor (TCR) therapy.