TACT projects

There are 11 PhD students working in the TACT project, investigating different questions related to the development of targeted anti-cancer therapies. We spoke to two PhD students at the University of Strasbourg, Lorenzo Turelli and Ilias Koutsopetras, about their research and its importance to the wider goal of developing more targeted anti-cancer therapies.

MULTI-COMPONENT REACTIONS

EU Researcher: What is the main focus in your research?

Ilias Koutsopetras: I am looking at the use of multi-component reactions for the conjugation of antibodies, where we add several small-molecule reactants to an antibody to produce a final antibody conjugate with precise modification sites.

EUR: Are you able to modify particular sites within the antibody for connection to a linker?

IK: One of the biggest challenges we face in developing antibody-drug conjugates (ADCs) is to identify which regions of an antibody we modify for connection to a chemical linker. We have made good progress in this.

EUR: How did you identify those regions?

IK: We tried out a lot of different conditions and conducted many optimisation trials, then we sent our conjugated antibodies to our analytical collaborators – the Cianferani lab, another member of our consortium in this project. They use a technique called native MS (Mass Spectrometry) to determine the conversion and average degree of conjugation of our antibodies – i.e. the number of sites modified by our multicomponent reaction. Then we move on to LCMS techniques to determine precisely the identity of these conjugation sites, using a technique called peptide mapping.

EUR: Did these results from the LCMS help guide your research?

IK: The results from the LCMS tell us in which regions of the antibody we had the conjugation. If we find specific sites of conjugation from our experiments, then we try to reproduce it and see if our method provides a repeatable result.

The nature of the conjugation site is important as it can have an impact on the

Keywords:Multicomponent

Lorenzo Turelli, PHD STUDENT

Keywords: Linker synthesis, antibody-drug-conjugates conjugated antibody’s behaviour in vivo: conjugation in the region responsible for antigen recognition – called the paratope –can lead to diminished affinity, making the antibody less able to recognize and bind its target antigen.