LifeArc study points towards expanded utility for antibody-drug candidates

A team of LifeArc scientists has had a key ‘proof of concept’ study published in ChemBioChem. The study explores the potential for the use of antibody-drug conjugates (ADCs) in extracellular, inhibitory applications – an extension of the existing use of ADCs to provide targeted cytotoxicity, usually as an anti-cancer therapy.

An ADC is an antibody-drug conjugate combining an antibody (providing targeting) with a small molecule component (providing the active effect). To date ADCs have been used to deliver cytotoxic small molecules to tumours. The LifeArc team hypothesised that the technique could be adapted to deliver a wider range of small molecules to more targets, both inside and outside of cells.

The experiment combined an antibody (REGA-3G12) with a small molecule ‘inhibitor’ (CGS27023A). CGS27023A inhibits the activity of an extracellular enzyme known as metalloproteinase-9 (MMP-9). Using the protocol described in their paper, the LifeArc team presented preliminary data demonstrating selective inhibition of MMP-9 using an ADC approach.

Why does this matter?

Extending the utility of ADCs has the potential to make previously difficult drug targets vulnerable to therapy.