Trivalent melanoma antigen peptide (Trp2-gp100-Trp1) (TgT)

The Trivalent melanoma antigen peptide, commonly abbreviated as TgT, is a synthetic fusion peptide designed for use in advanced cancer vaccines, specifically the proteolysis-targeting vaccine (PROTAV) or PROTAX platform. It consists of three immunodominant long peptide sequences derived from well-characterized melanoma-associated antigens: Tyrosinase-related protein 2 (Trp2), Glycoprotein 100 (gp100), and Tyrosinase-related protein 1 (Trp1). By combining these three antigens into a single trivalent construct, TgT aims to overcome tumor antigen heterogeneity and prevent immune escape by eliciting a multi-specific CD8+ T-cell response. In therapeutic applications, TgT is often conjugated to an E3 ligase recruiter (such as pomalidomide) to accelerate its intracellular processing and presentation by dendritic cells. This approach has shown significant potential in preclinical models for eradicating established melanoma tumors and enhancing the efficacy of immune checkpoint inhibitors.

Other names

Trp2-gp100-Trp1 fusion peptideTrivalent antigenic fusion peptideMelanoma trivalent antigenPROTAV-TgT antigenPROTAX-TgT antigen

The TgT peptide serves as a multivalent antigen source that, when incorporated into proteolysis-targeting vaccines, is targeted for E3 ligase-mediated ubiquitination and proteasomal degradation. This targeted proteolysis significantly enhances the efficiency of antigen cross-presentation on MHC class I molecules by antigen-presenting cells, leading to the robust activation of multi-specific CD8+ cytotoxic T lymphocytes against melanoma cells expressing Trp1, Trp2, or gp100.