Melanoma-associated antigen (Melanoma antigen recognized by T cells 1, Melanocyte protein PMEL, Tyrosinase) peptide-HLA-A*02:01 complex (MAA-HLA-A*02:01)

The target is a group of melanocyte differentiation antigens—Melanoma antigen recognized by T cells 1 (MART-1/Melan-A), Melanocyte protein PMEL (gp100), and Tyrosinase—presented as short peptides by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule [1, 3, 6]. These antigens are highly expressed in normal melanocytes and the majority of melanoma tumors, including cutaneous and uveal subtypes [1, 7]. Therapeutic strategies targeting these complexes include engineered T-cell receptor (TCR) T-cell therapies and bispecific T-cell engagers like tebentafusp [11, 15, 24]. By binding to the peptide-MHC complex, these drugs redirect the cytotoxic activity of CD8+ T cells specifically toward tumor cells [12, 14]. However, because these antigens are also present in normal melanocytes, treatment can lead to 'on-target, off-tumor' toxicities such as skin depigmentation (vitiligo) and ocular inflammation [13, 24, 29]. Patient eligibility is strictly defined by the presence of the HLA-A*02:01 allele and confirmed antigen expression in the tumor [11, 16].

Other names

Melanocyte differentiation antigensMART-1/gp100/TyrosinaseMelan-A/PMEL/TYRHLA-A*02:01-restricted melanoma antigensMelanoma-associated antigen peptide-MHC complexMART-1/gp100/Tyrosinase – HLA-A*0201–restricted TCRs

T-cell receptors (TCRs) or bispecific T-cell engagers bind to specific peptides derived from MART-1, gp100, or Tyrosinase presented by HLA-A*02:01 on the surface of melanoma cells, leading to T-cell activation and tumor cell lysis [11, 13, 24].