Challenges and opportunities in targeting the CD28/CTLA-4 pathway in transplantation and autoimmunity

Expert Opinion on Biological Therapy
Rebecca L Crepeau, M L Ford

Abstract

T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. Areas covered: This review discusses past, current and future biological therapies that have been utilized to block the CD28/CTLA-4 cosignaling pathway in the settings of autoimmunity and transplantation, as well the challenges facing successful implementation of these therapies. Expert opinion: The development of CD28 blockers Abatacept and Belatacept provided a more targeted therapy approach for transplant rejection and autoimmune disease relative to calcineurin inhibitors and anti-proliferatives, but overall efficacy may be limited due to their collateral effect of simultaneously blocking CTLA-4 coinhibitory signals. As such, current investigations into the potential of selective CD28 blockade to block the costimulatory potential of CD28 while exploiting the coinhibitory effects of CTLA-4 are promising. However, as selective CD28 blockade inhibits the activity of both effector and regulatory T cells, an important goal for the fu...Continue Reading

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Dec 12, 2018·Journal of Leukocyte Biology·Mohammad Afzal Khan, Talal Shamma
Oct 3, 2019·Proceedings of the National Academy of Sciences of the United States of America·Xiaoli WangDaved H Fremont
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Jul 10, 2021·Cell·Andreas Wieland, Rafi Ahmed
Dec 29, 2021·Immunological Medicine·Rafael Cardoso Maciel Costa SilvaBruno Ricardo Barreto Pires

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