T-cell receptor specific for Melanocyte protein PMEL (gp100) (gp100-specific TCR)

The T-cell receptor (TCR) specific for the gp100 (PMEL) antigen is a specialized immune receptor used in the targeted treatment of melanoma. gp100 is a lineage-specific protein involved in the biosynthesis of melanin and is highly expressed in both cutaneous and uveal melanoma cells (UniProt P17683). The TCR recognizes specific gp100 peptides, most notably the YLEPGPVTA epitope, when presented on the cell surface by the Human Leukocyte Antigen (HLA), typically HLA-A*02:01. Therapeutic applications involve engineering this TCR into a patient's T cells (TCR-T therapy) or using it as the targeting arm of bispecific molecules like Tebentafusp (Johnson et al., 2009, Blood). Tebentafusp, a first-in-class ImmTAC, redirects T cells to kill gp100-expressing tumor cells by bridging the TCR-HLA complex with the CD3 receptor on T cells (Nathan et al., 2021, NEJM). This approach has shown significant survival benefits in patients with metastatic uveal melanoma. However, because gp100 is also expressed in normal melanocytes, treatment can lead to on-target off-tumor toxicities such as skin rash and vitiligo (Damato et al., 2023, Eye).

Other names

gp100 TCRPMEL-specific T-cell receptorMelanoma-associated antigen gp100 TCRgp100-reactive T-cell receptorTCR-gp100

The target functions as a recognition unit for the gp100 antigen; drugs like Tebentafusp utilize a soluble version of this TCR to redirect T-cell cytotoxicity against melanoma cells by binding the gp100-HLA-A*02:01 complex and the CD3 receptor on T cells (Nathan et al., 2021, NEJM).