Targeting lymph nodes with liposomes bearing anti-HLA-DR Fab′ fragments

Abstract

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.

Hydrophobic Laminin-Related Peptides: Synthesis and Surface Properties

“…One of the most useful is that based on ligand/receptor recognition (4)(5)(6). This alternative requires the identification of some biological structures selectively expressed in the membrane of tumoral cells as, for instance, laminin whose receptors (integrins) are overexpressed in proliferant cells (7)(8)(9)(10).…”

Biodegradable Film for the Targeted Delivery of siRNA-Loaded Nanoparticles to Vaginal Immune Cells

“…HLA-DR is abundantly expressed on the cell membrane of antigen-presenting cells such as monocyte/macrophages and follicular dendritic cells (FDC). 31 The ability of anti-HLA-DR conjugated NP to enhance siRNA internalization in cells that express HLA-DR was evaluated using mature DCs (mKG-1) and VK2/E6E7 cells. Significantly higher uptake of FAM-siRNA-NP-Ab into mKG-1 cells was observed in comparison to cells treated with FAM-siRNA-NP, with a maximum uptake of FAM-siRNA-NP-Ab occurring after 4 h of treatment ( Figure 6).…”

In Vivo Anti-HIV Activity of the Heparin-Activated Serine Protease Inhibitor Antithrombin III Encapsulated in Lymph-Targeting Immunoliposomes

“…In addition, we studied the effects of ATIII treatment in rhesus macaques chronically infected with SIV. In a novel therapeutic approach, we used anti-HLA-DR antibodies engrafted into immunoliposomes to encapsulate hep-ATIII (termed ET-ATIII): it has been shown that these immunoliposomes specifically target HLA-DR positive cells in lymph nodes including monocytes, macrophages and activated CD4 + T lymphocytes, allowing concentration of therapeutic ATIII in the main cellular reservoirs of HIV and SIV [19]. Finally, we sought to understand the mechanism by which hep-ATIII exerts its antiviral activity.…”