Immunoliposome targeting to murine CD4+ leucocytes is dependent on immune status.
Immunoliposomes were prepared from dipalmitoylphosphatidylcholine, dimyristoylphosphatidylglycerol, biotinylated PE, and surface-linked avidin-biotinylated GK1.5 monoclonal rat (anti-mouse CD4) IgG or F(ab)2. Anti-CD4 immunoliposomes bound quantitatively to CD4+ PBMC's in vitro. Intravenous injection of mice with 1 mumol anti-CD4 immunoliposomes resulted in targeting to a significant proportion (> 75%) of CD4+ PBMCs. Repeated administration of anti-CD4 immunoliposomes induced significant levels of anti-GK 1.5 IgG Ab, with concomitant reductions in immunoliposome plasma t1/2 and targeting efficacy, and increased volumes of distribution. The immunogenicity of the immunoliposome was enhanced if GK1.5 F(ab)2 instead of IgG was used as the targeting ligand. Lipophilic poly(ethylene glycol) derivatives incorporated into the immunoliposomes did not affect targeting efficiency but significantly enhanced immunogenicity. These results demonstrate that IgG or F(ab)2 immunoliposomes are highly immunogenic and that targeting in vivo is conditional on the immune status of the host.
Phillips
N C
NC
Montreal General Hospital Research Institute, Quebec, Canada.
Gagne
L
L
Tsoukas
C
C
Dahman
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000276:immunology; D011092:Polyethylene Glycols / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008081:Liposomes; D010743:Phospholipids; D011092:Polyethylene Glycols