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The ProtEx Technology
ApoImmune's other platform technology, ProtEx, is a technology that enables recombinant immunoregulatory proteins to be placed on the surface of cells, tissues, organs, and synthetic surfaces in order to modulate the immune system. ProtEx, like ApoVax, is a recombinant protein-based vaccine therapy.
The lead product for the ProtEx technology is ApoFasL which improves current organ and tissue transplant therapies by protecting the transplant from being attacked by the recipient's immune system when transplanted into the body. An added benefit of the technology is that it also reduces the need for powerful immunosuppressive drugs with highly toxic effects that are required after transplantation. ApoImmune has licensed a component of its technology from a major pharmaceutical company, which management believes provides the Company freedom to practice its ApoFasL technology.
Preclinical proof-of-principle for both ProtEx and ApoFasL has been obtained using several different animal models for different transplant settings including heart and pancreatic islet transplantation. The first clinical application for ApoFasL will be as an insulin replacement therapy for the treatment of Type I Diabetes using ApoFasL-treated pancreatic islets. After completion of a non-human primate study, ApoImmune expects to begin a Phase I clinical trial.
The general ProtEx technology involves a proprietary chimeric protein which consists of a modified form of the biotin-binding protein streptavidin (SA) and a portion of an immunoregulatory protein that can regulate the immune system (refer to figure below). The presence of streptavidin allows for 1) the formation of a tetrameric immunoprotein able to crosslink its receptor on immune cells for potent signal transduction, and 2) the rapid attachment of the immunoregulatory proteins to biotinylated surfaces such as cell membranes.
Step 1: The "target" whether it is a cell, organ or tissue, or synthetic material, is coated with biotin, making it "biotinylated". In the figure below, a cell membrane (blue bi-layer) is modified with biotin (pink ovals). Biotinylation can be performed in vitro or in vivo.
Step 2: Then the chimeric ProtEx protein, which includes a portion of streptavidin, is presented to the biotin-coated surface, providing a long-lasting bond between the cell and the therapeutic protein. Represented below, the chimeric proteins consisting of core streptavidin (blue ovals) and immunological ligands (colored ovals) are used to bind to and decorate the biotinylated cell membranes.
ApoImmune's approach provides a powerful therapeutic effect because streptavidin, when bound to the cell surface through biotin, has the unique ability to aggregate active protein fragments at the cell surface. This aggregation causes the biological signals to be amplified. Once the ProtEx protein binds to the cell surface, it will engage its intended target on other cells. The ProtEx protein is attached reliably to the cell of interest and does not wander freely throughout the body. Because the treated cell carries the immunoregulatory protein directly to the target to be engaged, only a very small amount of the ApoImmune protein is necessary in order to cause a therapeutic effect.
This novel approach to generating novel proteins with potent immune activity and displaying them on the cell membrane for immunomodulation is a unique alternative to DNA-based approaches. DNA-based therapeutic approaches have several limitations, including the inefficient expression of proteins of interest, inadvertent genetic modifications in the host by the introduced recombinant DNA, and lack of specificity of expression. Furthermore, DNA-based therapeutic approaches are time and labor intensive. ProtEx technology presents an important technological advance over DNA-based gene expression for immunomodulation for the treatment of immune based disorders since this technology is practical, efficacious, safe, and cost/time effective with important therapeutic implications.
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