TECHNOLOGY
HETEROPOLYMER (HP) ANTIBODIES OVERVIEW
The HP antibody technology offers a unique approach to the management and treatment of infectious disease by utilizing the body’s own natural defense mechanisms to remove and destroy pathogens, such as bacteria and viruses. The HP technology uses a monoclonal antibody specific to a red blood cell receptor (CR1) that is chemically linked to a second antibody that binds a particular pathogen. After administration, the HP drug rapidly binds target pathogens to red blood cells and facilitates their clearance and destruction via liver macrophages. HP drugs are ideally suited to treat immunocompromised patients who typically have low levels of neutrophils and complement, important factors for fighting infection.
The HP technology is based upon principle of Immune Adherence (IA), a natural mechanism for clearance of blood-borne antigens via the red blood cell through a mechanism in which both activation of the complement system and the existence of pre-formed, circulating antibodies against the pathogen are necessary (Figure 1A). Even with both of these components, immune adherence is a very inefficient process.
Figure 1: Mechanism of pathogen clearance by Immune Adherence and Heteropolymers
View the HP Mechanism of Action animation
As shown in Figure 1B, an HP drug is composed of two monoclonal antibodies: one specific for the CR1 molecule on primate RBCs and a second antibody that is specific for the target pathogen or antigen. HP antibodies have been shown experimentally to bind a wide variety of pathogens, bacteria and viruses as well as other targeted proteins in the bloodstream to CR1 receptors and to transfer the pathogens to tissue macrophages in the liver where they are internalized and destroyed by lysosomal enzymes. An advantage of Heteropolymer Antibodies over single monoclonal antibodies alone is that HP drugs do not require lengthy development of antibodies that neutralize pathogen activity, only antibodies with strong binding affinity. Because CR1 is a privileged site on RBCs that has evolved for transport of immune complexes, the RBCs return unharmed to the circulation after clearance of the CR1-HP-pathogen complex, and continue to perform their normal physiological function. A clinical trial in humans has shown that after a single administration of an HP Antibody for treatment of systemic lupus erythematosus (SLE), no adverse toxicity or changes in hematological or chemistry parameters was observed .
While 90% of CR1 in humans is found on red blood cells, CR1 is also expressed at high levels on B cells, T cells, neutrophils, monocytes, and follicular dendritic cells. The expression of CR1 on leukocytes and follicular dendritic cells is especially interesting as these cells are known to play important roles in antigen presentation and immune responses. Recent data strongly suggests that an HP Antibody, by its direct binding of pathogens to CR1 receptors, potentiates antigen presentation and thereby also can act as a “vaccine” to induce immune responses to pathogenic antigens including bacteria, viruses and cancer antigens.