Targeting lymph nodes with liposomes bearing anti-HLA-DR Fab' fragments.
The ability of liposomes bearing anti-HLA-DR Fab' fragments to target cells expressing the human HLA-DR determinant of the major histocompatibility complex class II (MHC-II) has been evaluated and compared to that of conventional liposomes. Anti-HLA-DR immunoliposomes did not bind to HLA-DR-negative cells. In contrast, a high level of binding was observed following incubation of immunoliposomes with cells bearing important levels of human HLA-DR. The accumulation of conventional and murine anti-HLA-DR immunoliposomes in different tissues has been investigated following a single subcutaneous injection given in the upper back of C3H mice. Anti-HLA-DR immunoliposomes resulted in a much better accumulation in the cervical and brachial lymph nodes when compared to conventional liposomes. The accumulation in the liver was similar for both liposomal preparations, whereas an approximately twofold decrease in accumulation was observed for immunoliposomes in the spleen. Given that HLA-DR surface marker is expressed on monocyte/macrophages and activated CD4+ T lymphocytes, the primary cellular reservoirs of the human immunodeficiency virus (HIV), the use of liposomes bearing surface-attached anti-HLA-DR could constitute a convenient strategy to more efficiently treat this debilitating retroviral disease. Moreover, the reported incorporation of high amounts of host-encoded HLA-DR proteins by HIV particles renders the use of liposomes bearing anti-HLA-DR antibodies even more attractive.
Dufresne
I
I
Centre de Recherche en Infectiologie, Université Laval, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, 2705 Blvd. Laurier, Québec, QC, Canada.
Désormeaux
A
A
Bestman-Smith
J
J
Gourde
P
P
Tremblay
M J
MJ
Bergeron
M G
MG
D000818:Animals; D004337:Drug Carriers; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008081:Liposomes; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010714:Phosphatidylethanolamines
D004337:Drug Carriers; D006684:HLA-DR Antigens; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D010714:Phosphatidylethanolamines; C033182:N-(4-(4-maleimidophenyl)butyryl)phosphatidylethanolamine