PROTAX-TgT

PROTAX-TgT (also referred to as PROTAV-TgT) is an experimental proteolysis-targeting vaccine (PROTAX) developed for the treatment of melanoma. It is a modular conjugate consisting of a trivalent melanoma-associated antigen—a tandem peptide fusion of Trp2 (tyrosinase-related protein 2), gp100 (glycoprotein 100), and Trp1 (tyrosinase-related protein 1)—linked to an E3 ubiquitin ligase-binding ligand, such as the cereblon (CRBN) ligand pomalidomide. The vaccine is designed to be co-delivered via lipid nanoparticles (LNPs) alongside immunostimulant adjuvants. Its mechanism of action involves hijacking the ubiquitin-proteasome system within antigen-presenting cells (APCs). By recruiting an E3 ligase into proximity with the vaccine antigens, PROTAX-TgT facilitates rapid ubiquitination and subsequent proteolytic processing by the proteasome. This enhanced processing promotes the cross-presentation of the antigens on MHC class I molecules, significantly potentiating the quantity and quality of antigen-specific CD8+ T cell responses. Preclinical studies in melanoma-bearing mice have shown that PROTAX-TgT, especially in combination with immune checkpoint blockade (ICB), can remodel the tumor immune microenvironment, achieve complete tumor regression, and extend survival.

Other names

Proteolysis-targeting vaccine-TgTTrp2-gp100-Trp1 PROTAXTrp-2-gp100-Trp1 PROTAXTrp 2-gp100-Trp1 PROTAXPROTAV-melanoma