Dopachrome tautomerase (Tyrosinase-related protein 2) (TRP-2)

Dopachrome tautomerase, also known as Tyrosinase-related protein 2 (TRP-2), is a key enzyme in the melanin biosynthesis pathway, specifically catalyzing the conversion of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid [UniProt P40126]. It is primarily expressed in melanocytes and is highly prevalent in melanoma cells, making it a well-characterized tumor-associated antigen (TAA) [PubMed 8642301]. In immunotherapy, TRP-2-derived peptides are presented by Major Histocompatibility Complex (MHC) molecules to T-cell receptors (TCRs), triggering a cytotoxic immune response against the tumor [PubMed 11015445]. Various therapeutic strategies, including peptide vaccines, DNA vaccines, and TCR-engineered T-cell therapies, have been developed to target TRP-2 in patients with advanced melanoma [ClinicalTrials.gov]. While effective in inducing anti-tumor immunity, targeting TRP-2 carries a risk of on-target, off-tumor toxicity, most commonly manifesting as vitiligo due to the destruction of healthy melanocytes [PubMed 15155838].

Other names

DCTTRP2Dopachrome delta-isomeraseL-dopachrome tautomeraseTyrosinase-related protein 2

Induction of a cytotoxic T-lymphocyte (CTL) response against cells presenting TRP-2-derived peptides on MHC Class I molecules, leading to targeted lysis of melanoma cells.