Mechanism of action, in vitro validation, and the scientific foundation of the TBDS platform
Each TBDS construct is a single recombinant fusion protein combining three functional modules: the PS14 tumor-targeting delivery module (TDM), an MMP-2/9 cleavable linker, and the cytotoxic payload (CTP).
In the unactivated state, the TDM shields the CTP — preventing off-target toxicity. Upon encountering the tumor microenvironment's elevated MMP-2/9, the linker is cleaved and CTP is released to physically destroy the cancer cell membrane through pore formation.
Gel electrophoresis and cytotoxic bioassay confirm efficient MMP-2/9-mediated proteolytic cleavage of the TBDS linker — the molecular mechanism underlying selective tumor activation.
The unactivated PS14-CTP complex demonstrates zero toxicity in the absence of MMP-2/9. This is not merely reduced toxicity — it is complete abolition, confirmed by both CelTox and RealTime-Glo assays. Healthy tissue, lacking elevated MMP-2/9, would remain completely protected.
Xenograft studies show no body weight loss across TBDS-treated groups (ISB-20, ISB-21 at 5 mg/kg), in contrast to the systemic toxicity profile typical of chemotherapeutic agents at comparable doses. See Pipeline & Data for full in vivo results.
Explore the full pipeline — four constructs, in vivo validation of efficacy in breast and prostate cancers, and the EGFR-targeted modular expansion.