By the end of reporting period 1, the following achievements can be underlined:
Workpackage 1 (WP1): we successfully identified and analyzed more than 20 different antibodies from various sources. By modifying sequences from these antibodies, we generated anti-OSE single-chain variable fragment (scFv) antibodies that were highly specific for their target molecules, as first demonstrated by ELISA and competition assays. These scFvs effectively bound to atherosclerotic plaques in both mice and humans, specifically targeting lipid-rich, acellular regions of plaques in advanced lesions.
Workpackage 2 (WP2): we explored the treatment modalities of IL-2IT administration and succeeded in generating valuable insights by developing two gene expression systems (AAVs and mRNA)
also explored the treatment modalities of IL-2IT administration. In fact, during this initial phase of the project, we successfully generated valuable insights with this regard by developing two gene expression systems (AAVs and mRNA)
Workpackage 3 (WP3): we have developed a pipeline for the preclinical evaluation of IL-2IT candidates, including safety, pharmacokinetics/pharmacodynamics (PK/PD), and biodistribution studies in animal models. Comprehensive PK/PD studies are being conducted in mice under both normal and inflammatory conditions. To date, four IL-2ITs have been fully characterized.
Workpackage 4 (WP4): initial results obtained in animal models are very promising showing a significant and selective increase in T regulatory (Treg) cells following administration of IL-2IT.
In addition, a successful arthritis model has been developed for efficacy studies.
Workpackage 5 (WP5): regarding dissemination and valorisation, members of the consortium have organized the 3rd edition of “The Promise of Interleukin-2 Therapy for Autoimmune and Inflammatory Diseases, Allergy, Transplantation, and Cancer” an international meeting, held from September 4 to 7, 2024, in Paris and which brought together leading scientists and pharmaceutical companies.
Workpackage 6 (WP6): this WP is dedicated to the management and governance of the project which has been successfully implemented and ensures smooth running of the activities throughout its duration.
Overall, TiilT is progressing well towards its objectives. In the coming period, a maximum of four IL-2IT candidates will be selected by consensus for further evaluation in animal models of cardiovascular diseases.
