Premelanosome protein (gp100) and Melanoma antigen recognized by T cells 1 (MART-1) (gp100/MART-1)

gp100 (Premelanosome protein, PMEL) and MART-1 (Melanoma Antigen Recognized by T cells 1, Melan-A) are two distinct melanocyte differentiation antigens (MDAs) that are frequently targeted in melanoma immunotherapy [5, 9]. Both proteins are primarily expressed in normal melanocytes and are highly overexpressed in the majority of cutaneous and uveal melanomas, making them valuable tumor-associated antigens for diagnostic and therapeutic purposes [1, 3, 4]. gp100 is a glycoprotein involved in the formation of the fibrillar matrix within melanosomes, while MART-1 is a transmembrane protein essential for the stability and trafficking of gp100 [14, 16]. Because these antigens are presented as peptides on the cell surface by MHC molecules, they are targeted by various modalities, including peptide vaccines, TCR-engineered T-cell therapies, and bispecific T-cell engagers [8, 11, 15]. Tebentafusp (Kimmtrak) is a first-in-class bispecific protein that redirects T cells to target gp100-expressing cells in HLA-A*02:01-positive patients with metastatic uveal melanoma [10, 20]. Therapeutic intervention against these targets often results in 'on-target, off-tumor' toxicities, such as vitiligo and cutaneous rashes, due to the presence of these antigens in normal skin melanocytes [13, 21]. Although often grouped together in clinical research, they are encoded by separate genes (PMEL and MLANA) and represent two distinct molecular targets [6, 7].

Other names

PMELMLANAMelan-APmel17SILVSilver locus protein homologME20Melanoma-associated antigen

T-cell redirection via bispecific T-cell engagers, active immunization via peptide vaccines, and adoptive cell transfer using TCR-engineered T cells.