TEGOPRUBART’s Multiple Mechanisms of Action Could Help Effectively Manage Immune Response
Tegoprubart targets the CD40 ligand (also known as CD40L and CD154). Blocking CD40L has been shown to inhibit multiple costimulatory receptors including CD40 and CD11, key components of how immune cells communicate with one another. Blocking CD40L also increases polarization of lymphocytes into Tregs, a specialized subpopulation of T cells that act to suppress immune response. We believe these multiple mechanisms can create a more tolerogenic environment for organ and cellular transplants, providing the potential to protect and increase the lifespan of transplanted organs. They may also have the ability to modulate immune response in autoimmune and neurogenerative diseases such as ALS.
The CD40L Ligand Pathway Is a Promising Target for Increasing Transplant Function and Longevity
The central role of CD40L signaling in generating pro-inflammatory responses makes it an attractive candidate for therapeutic intervention in the protection of transplanted organs and the prevention of transplant rejection, as well as modulating immune responses in autoimmune disease, and in neuroinflammation. Blocking the activation of the CD40L pathway has been shown to slow disease progression and pathology in preclinical models of autoimmunity and neurodegeneration, and to prevent acute and long-term allograft transplant rejection in multiple animal species.
Our Immune System Communicates to Keep Us Healthy. Sometimes It “Talks” Too Much.
CD40/CD40L Pathway and Tegoprubart Site of Action
The interaction of CD40 with CD40L on immune cells mediates the activation of the co-stimulatory immune pathway to silence the crosstalk between the innate and adaptive immune systems that amplify an uncontrolled inflammatory response. The engagement of these receptors also plays a pivotal role in immune system activation by mediating both antibody and cellular immune responses.
The initiation of a robust immune response is mitigated by costimulatory signaling when CD40L binds costimulatory receptors, such as CD40, on antigen presenting cells. These cells are simultaneously presenting foreign peptides on their major histocompatibility complex (MHC) receptors to the T cell receptor on lymphocytes. The interaction of CD40L and CD40 results in clonal expansion, antibody production, and secretion of pro-inflammatory cytokines that amplify an immune response.
Importantly, blocking CD40L is not associated with the lymphopenia seen in many immunosuppressive drugs.