Tebentafusp (IMCgp100) is a protein that specifically targets gp100 and consists of a soluble T-cell receptor functionally fused to an anti-CD3 immune effector Tebentafusp has potential anti-tumor activity, induces the production of inflammatory cytokines and cytolytic proteins, and can be used to study unresectable or metastatic uveal melanoma.

Tebentafusp is an ImmTAC that recognizes a peptide derived from the HLA-A*0201-expressed melanoma-specific protein gp100. Tebentafusp was able to stimulate cytotoxic degranulation activity of peripheral blood mononuclear cells (PBMC) against Mel526 cells after 16 hours of treatment at concentrations of 31 pM, 82 pM, and 131 pM, but did not have this effect on gp100-negative A375 cells. When treated at 100 pM for 0-50 h, Tebentafusp was able to mediate the killing of CD8+ T cells, even in the presence of regulatory T cells, and activate caspase 3/7 within 40-48 h. Similarly, when treated at 100 pM for 0-80 h, Tebentafusp was able to trigger the cytotoxic degranulation activity of a subset of CD4+ T cells against melanoma cell cytolysis. At 1, 12, 31, 82 and 131 pM for 24 h or 96 h, Tebentafusp increased granzyme B levels and induced extensive release of cytokines and chemokines from CD4+ and CD8+ T cells. [1]

In a mouse melanoma model, Tebentafusp administered intravenously at a dose of 10 μg/kg significantly inhibited tumor growth. [2]