T-cell receptor recognizing HLA-presented TRP-2 and gp100 epitopes (TCR (TRP-2/gp100))

The T-cell receptor (TCR) recognizing HLA-presented TRP-2 and gp100 epitopes is a therapeutic receptor used in adoptive cell transfer (ACT) for the treatment of metastatic melanoma. These TCRs are engineered to bind specifically to peptides derived from Tyrosinase-related protein 2 (TRP-2) and Glycoprotein 100 (gp100), which are melanoma-associated antigens (MAAs) presented by the HLA-A*02:01 molecule. TRP-2 and gp100 are enzymes and proteins involved in the melanogenesis pathway and are highly expressed in both malignant melanoma cells and normal melanocytes. By modifying a patient's T cells to express these TCRs, the immune system is redirected to recognize and eliminate tumor cells. However, because these antigens are also present in healthy tissues such as the skin, eyes, and inner ear, therapy can lead to on-target, off-tumor toxicities including vitiligo, uveitis, and hearing loss. Clinical trials have demonstrated the potential for significant tumor regression using these TCR-based approaches, often in combination with lymphodepleting chemotherapy and interleukin-2 (IL-2) support.

Other names

TRP-2-specific T-cell receptorgp100-specific T-cell receptorMelanoma-associated antigen-specific TCRHLA-A2-restricted TRP-2/gp100 TCRPMEL-specific T-cell receptorDCT-specific T-cell receptor

Engineered T cells expressing these TCRs bind to specific peptide-MHC complexes (derived from TRP-2 or gp100) on the surface of melanoma cells, triggering T-cell activation, the release of cytotoxic cytokines, and direct tumor cell lysis via the perforin/granzyme pathway.