TR3 biologics for the treatment of cancer
The TR3 molecule is a unique bioactive trimer of TNF superfamily TRAIL (TNF-related apoptosis-inducing ligand, designated TR3) that has been developed with a highly targeted affinity for cancer cells. This unique fused TR3 overcomes historical challenges faced by TRAIL therapies. When fused with a mesothelin peptide (Meso64-TR3), it directly binds MUC16 with high affinity and delivering a strong apoptosis signal, resulting in efficient cancer cell death. The MUC16-targeted Meso64-TR3 molecule exhibits highly aggressive killing efficacy of cancer cells compared to healthy cells in vitro and exhibits remarkably specific action compared to existing recombinant TRAIL technologies.
The fusion of TR3 to mesothelin-specific single-chain antibody (scFv) produces a complex that targets mesothelin-positive cancer cells. Fully humanized variants have been developed and showed greatly improved in vitro targeting and elimination of mesothelin-positive cancer cells. In addition, this platform technology is open to conjugation with other molecules, for directed targeting and treatment of cancer cells expressing different tumor biomarkers.