Submitted April 19, 2006
Accepted September 15, 2006
Comparison of the effects of antibody-coated liposomes,
IVIG and anti-RBC immunotherapy in a murine model of
passive chronic immune thrombocytopenia
Rong Deng and Joseph P. Balthasar*
Dept of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY
* Corresponding author; email: jb{at}acsu.buffalo.edu.
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 anti-methotrexate antibody (AMI)-coated liposomes and intravenous immunoglobulin (IVIG)-coated liposomes (15, 30, 60 µmol lipid/kg) were compared to the effects of IVIG (0.4, 1, 2 g/kg) and anti-red blood cell (RBC) monoclonal antibody immunotherapy (TER119, 5, 15, 25 and 50 µg/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 µg TER119/mouse versus 160±34% for 2 g/kg IVIG, 88±36% for 60 µmol lipid/kg AMI-coated liposomes, and 80±25% for 60 µmol lipid/kg IVIG-coated liposomes). However, the effects of TER119 were associated with severe hemolysis, as TER119 decreased RBC counts by ~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.
