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The ProtEx™ Technology
ApoImmune's second 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 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 conjugation 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 proteins 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.
The lead product for the ProtEx™ technology is Apo195 which enhances and improves upon current transplant therapies by inducing immune tolerance to the transplants while reducing the long-term use of potent immunosuppressive drugs. Proof of principle for Apo195 has been obtained for organ, tissue, and hematopoietic stem cell transplant settings. The first clinical application for Apo195 will be as an insulin replacement therapy for the treatment of Type I Diabetes.
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