T-cell receptor recognizing tyrosinase-related protein 2-derived peptide–MHC complexes (TCR-Trp2)

The T-cell receptor (TCR) recognizing tyrosinase-related protein 2 (Trp2)-derived peptide–MHC complexes is a specialized immune receptor used in adoptive T-cell therapy for melanoma. Trp2, also known as dopachrome tautomerase (DCT), is a lineage-specific enzyme involved in melanin synthesis that is highly expressed in both normal melanocytes and melanoma cells. By engineering a patient's T-cells to express a high-affinity TCR specific for a Trp2 epitope (commonly Trp2:180-188) presented by MHC class I molecules (such as HLA-A*02:01), the immune system can be redirected to identify and destroy malignant cells. This target is particularly relevant in the context of TCR-T cell therapy, where the goal is to overcome the limitations of the endogenous immune repertoire against self-antigens. However, because Trp2 is also expressed in healthy melanocytes, therapeutic interventions targeting this complex carry risks of on-target off-tumor toxicities, including vitiligo and inflammatory conditions of the eye and ear.

Other names

Trp2-specific T-cell receptorDopachrome tautomerase-specific T-cell receptorDCT-specific T-cell receptorTCR recognizing Trp2:180-188Tyrosinase-related protein 2-specific TCR

Adoptive cell transfer of T-cells engineered to express a specific T-cell receptor (TCR) that recognizes the Trp2 peptide presented by MHC molecules, leading to targeted lysis of Trp2-expressing tumor cells.