Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia.
The present work evaluated antibody-coated liposomes as a new treatment strategy for immune thrombocytopenic purpura (ITP) through the use of a mouse model of the disease. Effects of antimethotrexate antibody (AMI)-coated liposomes and intravenous immunoglobulin (IVIG)-coated liposomes (15, 30, 60 micromol lipid/kg) were compared with the effects of IVIG (0.4, 1, 2 g/kg) and anti-red blood cell (anti-RBC) monoclonal antibody immunotherapy (TER119, 5, 15, 25, and 50 microg/mouse) on MWReg30-induced thrombocytopenia. Each treatment was found to attenuate thrombocytopenia in a dose-dependent manner and, consistent with previous work, IVIG was found to increase antiplatelet antibody clearance in a dose-dependent manner. TER119 demonstrated greater effects on thrombocytopenia relative to other therapies (peak platelet counts: 224% +/- 34% of initial platelet counts for 50 microg TER119/mouse versus 160% +/- 34% for 2 g/kg IVIG, 88% +/- 36% for 60 micromol lipid/kg AMI-coated liposomes, and 80% +/- 25% for 60 micromol lipid/kg IVIG-coated liposomes). However, the effects of TER119 were associated with severe hemolysis, as TER119 decreased RBC counts by approximately 50%. The present work demonstrated that antibody-coated liposomes attenuated thrombocytopenia in this model at a much lower immunoglobulin dose than that required for IVIG effects and, in contrast with TER119, antibody-coated liposomes increased platelet counts without altering RBC counts.
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; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D007167:Immunotherapy; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D013921:Thrombocytopenia / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
D000906:Antibodies; D008081:Liposomes