T cell receptor specific for Tyrosinase-related protein 2 (180-188) peptide-MHC complex (TRP-2-specific TCR)

The T cell receptor (TCR) specific for the Tyrosinase-related protein 2 (TRP-2) peptide fragment 180-188 (SVYDFFVWL) presented on MHC class I (typically HLA-A*02:01) is a critical component in targeted immunotherapy for melanoma (Parkhurst et al., 1998, Cancer Research). TRP-2, also known as dopachrome tautomerase (DCT), is a melanocyte differentiation antigen that is frequently overexpressed in melanoma cells, making it an attractive target for adoptive cell therapy (Wang et al., 1996, Journal of Experimental Medicine). When engineered into patient-derived CD8+ T cells, this specific TCR enables the immune system to recognize and eliminate malignant cells expressing the TRP-2 antigen (Noppen et al., 2000, International Journal of Cancer). This interaction triggers T cell activation, proliferation, and the release of cytotoxic granules like granzymes and perforins to induce apoptosis in the target tumor cells (Restifo et al., 2012, Nature Reviews Immunology). Therapeutic strategies often involve the use of TCR-engineered T cells (TCR-T), where a patient's own T cells are modified to express this specific receptor to overcome immune tolerance (Morgan et al., 2006, Science). Clinical challenges include the potential for on-target, off-tumor toxicity, as the TCR may also target healthy melanocytes in the skin, hair, and eyes, leading to conditions like vitiligo or uveitis (Bowne et al., 2000, Cancer Research). Research continues to refine the affinity of these receptors to balance potent anti-tumor activity with manageable safety profiles in the context of MHC-restricted presentation (Johnson et al., 2009, Blood).

Other names

TRP-2 TCRDCT-specific T cell receptorTyrosinase-related protein 2-specific TCRSVYDFFVWL-specific TCRTRP-2:180-188-specific T cell receptor

Adoptive cell transfer of T cells engineered to express a high-affinity T cell receptor (TCR) that recognizes the TRP-2 (180-188) peptide presented by MHC class I molecules, leading to targeted lysis of tumor cells.