Tebentafusp (IMCgp100), a first in class immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC) for HLA-A*02:01 positive uveal melanoma: Product review.

Tebentafusp (IMCgp100, Kimmtrak) is a first-in-class Immune mobilizing monoclonal T-cell receptors against cancer (ImmTAC). ImmTAC are fusion proteins comprising an affinity-enhanced soluble T-cell receptor (TCR) against a specific peptide-HLA complex and an anti-CD3 single-chain variable fragment (scFv). Tebentafusp binds gp100(280-288) peptide from the melanocyte lineage-specific protein Glycoprotein 100 presented by HLA-A*02:01; concurrently, it engages CD3 on polyclonal T-cells leading to T-cell activation, and melanoma cell lysis. In the phase III IMCgp100-202 trial, tebentafusp significantly improved overall-survival versus investigator's choice, establishing it as a first-line treatment for HLA-A*02:01-positive advanced uveal melanoma. The safety profile is characterized by predictable on-target effects, mainly cytokine release syndrome and skin reactions, both diminishing over time. Tebentafusp validated ImmTAC as a novel class of TCR-based biologics targeting intracellular antigens. Ongoing research explores tebentafusp in other settings, including cutaneous melanoma. Other ImmTACs, e.g. brenetefusp is being developed, underscoring the potential of this modality in cancer immunotherapy.