Primate erythrocyte (E) complement receptor (CR1) as an anchor site for bispecific-based therapies to clear pathogens or autoantibodies safely from the circulation.
We have prepared cross-linked, bispecific complexes [heteropolymers (HP) and antigen-based heteropolymers (AHP)] that facilitate complement-independent binding of target model pathogens or autoantibodies to primate erythrocytes (E) via complement receptors (CR1). The method is based on using monoclonal antibodies (mAb) specific for CR1 that either are cross-linked to an mAb specific for a prototype pathogen (e.g., IgE) or are cross-linked to an autoantigen (e.g., dsDNA) that is recognized by circulating pathogenic autoantibodies in the autoimmune disease systemic lupus erythematosus (SLE). The underlying assumption in this research is that complexed ligands containing IgG bound to primate E CR1 should be recognized and processed via the same mechanism by which complement-opsonized immune complexes bound to E CR1 are cleared from the circulation and phagocytosed in the liver and spleen. Our work in experimental monkey models has demonstrated that binding of substrates to primate E via this method does indeed lead to the safe and rapid clearance of the target pathogens or autoantibodies from the circulation, without any lysis or loss of the E. Although a number of questions must still be resolved, it may be possible to generalize these findings and use this CR1-based approach to develop a simple noninvasive bispecific therapy that can be used to clear pathogens or autoantibodies from the circulation.
Taylor
R P
RP
Department of Biochemistry, University of Virginia School of Medicine, Charlottesville 22908, USA.
Ferguson
P J
PJ
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D004912:Erythrocytes / Q000378:metabolism*; D018796:Immunoconjugates / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000502:physiology; D008253:Macaca mulatta; D008264:Macrophages / Q000502:physiology; D008657:Metabolic Clearance Rate; D012157:Mononuclear Phagocyte System / Q000502:physiology*; D010587:Phagocytosis; D011951:Receptors, Complement / Q000378:metabolism*; D013154:Spleen / Q000502:physiology
D018033:Antibodies, Bispecific; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D018796:Immunoconjugates; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011951:Receptors, Complement; D007073:Immunoglobulin E