Investigation of antibody-coated liposomes as a new treatment for immune thrombocytopenia.
Immune thrombocytopenia (ITP) is an autoimmune disease that is mediated by anti-platelet antibodies. It is believed that anti-platelet antibody-opsonized platelets are eliminated through Fcgamma receptor-mediated and complement-mediated phagocytosis by macrophages of the reticuloendothelial system (RES). Polyclonal pooled immunoglobulin with high titer for the D-antigen of erythrocytes (i.e., anti-D) has been successfully used to ameliorate ITP. Based on the pathogenesis of ITP and based on the successful application of anti-D for the treatment of ITP, we hypothesized that antibody-coated liposomes may be used to inhibit Fcgamma receptor-mediated and complement-mediated phagocytosis, thereby increasing platelet counts in ITP. To test this hypothesis, we have developed a liposome preparation that is coated with a model monoclonal IgG1 antibody. Antibody-coated liposomes were found to inhibit complement deposition and macrophage phagocytosis in vitro. Furthermore, antibody-coated liposomes were also found to attenuate thrombocytopenia in a rat model of ITP, in a dose-dependent manner. The results suggest that antibody-coated liposomes may be used as 'decoy particles' to competitively inhibit the destruction of antibody-coated platelets; thus, antibody-coated liposomes may have value in the treatment of ITP.
Deng
Rong
R
Department of Pharmaceutical Sciences, 457B Cooke Hall, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
Balthasar
Joseph P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology*; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000276:immunology
D000911:Antibodies, Monoclonal; D003176:Complement C3; D007074:Immunoglobulin G; D008081:Liposomes; D011961:Receptors, Fc