A novel class of drug: Antibody Drug Radioisotope Conjugates (ADRC) for treating advanced cancers – 2in1-ADRC

2in1-ADRC project aims at the development of a new class of therapeutic agents combining advantages of Antibody Drug Conjugates (ADC) and those of Targeted Radiopharmaceuticals (TRP) and compensating for their respective weaknesses, in order to ensure selective delivery of the killing payload at the tumor site while avoiding as much as possible off-target payload release, thus reducing deleterious side effects. A versatile platform will be used for modular conjugation on bispecific biovectors of i) a DOTA chelator for either 177Lu or 225Ac for beta- or alpha therapy respectively, ii) a cytotoxic drug. Proof of concept of the added value of loading a single targeting ligand with two different killing payloads will be achieved through in vitro and in vivo studies of antitumor efficacy of bispecific dual payload bioconjugates, so-called ADRC, in the context of two clinically relevant case studies. We expect that the outcomes of this project will pave the way for the design of a next generation of targeted therapeutic agents, with complementary activities on different cell subtypes and tumor settings, resulting in more potent antitumor efficacy than standard ADC or TRP on aggressive or advanced cancers. This approach will also enable to lower the respective dosing of each individual payload for a better tolerance. Beyond this project, the skills and knowledge developed by the partners will be implemented in a broader R&D program to prepare for transfer to the clinic.