Bernard Vanhove - Development of CD28 antagonists to differentially impact effector versus regulatory cells post transplantation

"CD28 blockade" has been long referred to as use of CTLA4-Ig. However it has now been recognized that CTLA4-Ig, which actually binds CD80/86, inhibits CD28-mediated costimulation as well as CTLA-4 and PDL-1 co-inhibitory signals that are important immune checkpoints also involved in the control of Treg suppression. The development of non-agonist monovalent anti-CD28 antibodies made it possible to study the biological and therapeutic impacts of "selective CD28 blockade". Firstly, selective CD28 antagonists are able to differentially control effector and regulatory T cells. Second, they are very effective at blocking memory T cell responses, which are under the dependency of CD28 and CTLA-4/PD-1. In vivo, selective CD28 antagonists have demonstrated efficacy in preclinical primate models of heart, kidney and bone marrow transplantation, as well as in autoimmune encephalomyelitis, skin inflammation and collagen arthritis models. A major finding drawn from these experiments is the possibility to induce an antigen-specific hyporesponsiveness, the mechanisms of which stays to be further defined. Selective CD28 antagonists have initiated their clinical development and might become a new therapeutic paradigm in autoimmunity and transplantation.

Intervenant

Ph.D Thesis in Science, UCL (Belgium), Co-founder of Effimune and CEO since July 2014. He had an international Scientific career in particular at the Sandoz Research Institute, Vienna, Austria. Research Director at CNRS (The National Center for Scientific Research), at INSERM (the French National Institute of Health and Medical Research) within ITUN (Centre of Research in Transplantation and Immunology), his activities also took place within the CESTI (European Center of Transplantation and Immunotherapy Sciences). Award winner of France Transplant in 2013, prize awarded for the pharmacological and preclinical trials for immunology efficacy and for product tolerance of the FR104 (a monoclonal antibody fragment which is a specific antagonist of CD28). He was also the coordinator of the FP7 proposal "TRIAD" in auto immune diseases (Tolerance Restoration in Autoimmune Diseases) and is the author of over 80 international publications in immune restoration.

2^nd IGO meeting

La seconde édition des conférences organisées par le Labex IGO (IGO meeting) s’est déroulée les 21 et 22 avril 2016 à la Faculté de pharmacie de Nantes. Cette conférence a rassemblé 160 spécialistes de l’immunologie, de la transplantation et de l’oncologie. Des orateurs français et étrangers (USA, Grande-Bretagne, Pays-Bas, Espagne, Italie, Suisse) sont venus exposer leurs travaux et les dernières avancées dans leurs domaines de recherche. Des sessions (communications orales et posters) étaient également réservées aux jeunes chercheurs pour qu’ils puissent présenter leurs travaux et ainsi favoriser les échanges avec leurs collègues et les chercheurs séniors. Ce 2^nd IGO meeting, en créant un environnement propice à l’initiation de nouvelles collaborations à l’intérieur et au-delà du périmètre du Labex IGO, a été un vrai succès scientifique.