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SP0016 Revisiting Anti-CD28 Therapy
  1. B. Vanhove
  1. INSERM/Effimune, Nantes, France

Abstract

“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 checkpoint inhibitors 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”. First, 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 in primates 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.

Disclosure of Interest B. Vanhove Shareholder of: Shareholder of Effimune

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