|
Overview
ApoImmune takes advantage of two sets of proteins with opposing functions in the regulation of the immune system. The first set, exemplified by ApoFasL, is involved in immuno-downregulation and tolerance to self antigens. The second set of proteins are referred to as co-stimulatory proteins and are receptor-ligand pairs expressed on the surface of T cells and antigen presenting cells (APCs). Co-stimulation is crucial to the development of a productive immune response and is necessary for immune homeostasis, T cell proliferation, differentiation and survival.
Immune co-stimulatory signals transduced via the tumor necrosis factor receptor (TNFR) and CD28 family members modulate innate, adaptive, and regulatory immunity. As such, select members of these families serve as promising targets for the development of immunotherapies. Agonistic antibodies (Abs) to some co-stimulatory receptors have demonstrated therapeutic efficacy in various cancer and infection models. However, treatment with agonistic Abs may not produce the same signaling and response as the natural ligand to the receptor, and often results in severe toxicity. Therefore, agonistic ligands for these receptors may have better efficacy as components of immunotherapies than the agonistic Abs. However, the major limitation of using these proteins is that they function as cell surface proteins and have minimal to no activity in soluble, monomeric forms.
In answer to this, ApoImmune has developed a library of chimeric proteins composed of the extracellular domain of immunomodulatory ligands fused to the protein streptavidin (SA). SA is a tetrameric protein and when a partner protein is fused to SA the resulting chimeric protein also forms tetramers and oligomers under physiological conditions. ApoImmune has demonstrated that its SA-chimeric proteins have potent immunomodulatory activities. The following sections will highlight the lead candidate immunotherapies.
|
|
|
