PhD thesis of Emmanuel Douez (Novel immunoconjugates against TNBC)

Summary

An ADC (antibody-drug conjugate) is a targeted vectorized therapy resulting from the grafting of a powerful cytotoxic agent onto a therapeutic antibody via a chemical linker. Despite being targeted therapies, toxicities are often observed. These could be associated with the binding of the Fc portion of the IgG to Fc-Rn and FcγR receptors. The efficacy of ADCs may be limited by their large size (150 kDa), associated with reduced penetration into tumors. For this reason, new antibody conjugate formats are being designed to overcome these limitations. This thesis is part of an active collaboration between three teams in Tours (BioMAP, CEPR, and NMNS) with complementary skills in antibody engineering, chemical link development, in vitro and in vivo biological evaluation, and ADC stability studies. It is in these last two areas that the thesis's objectives lie more precisely, namely to develop ADCs with innovative alternative formats and bonds.

Project: BASTET (APR-IR 2020, Coord N. Aubrey, ISP, Tours)

Papers:

• Douez et al, J Control Release, 2024, doi:10.1016/j.jconrel.2024.01.012
• Auvert et al, J Med Chem, 2025, doi:10.1021/acs.jmedchem.5c01184