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 co mplex class II (MHC-II) has been evaluated and compared to that of conventi onal liposomes. Anti-HLA-DR immunoliposomes did not bind to HLA-DR-negative cells. In contrast, a high level of binding was observed following incubat ion 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 in jection given in the upper back of C3H mice. Anti-HLA-DR immunoliposomes re sulted in a much better accumulation in the cervical and brachial lymph nod es when compared to conventional liposomes. The accumulation in the liver w as similar for both liposomal preparations, whereas an approximately twofol d decrease in accumulation was observed for immunoliposomes in the spleen. Given that HLA-DR surface marker is expressed on monocyte/macrophages and a ctivated CD4+ T lymphocytes, the primary cellular reservoirs of the human i mmunodeficiency virus (HIV), the use of liposomes bearing surface-attached anti-PILE-DR could constitute a convenient strategy to more efficiently tre at this debilitating retroviral disease. Moreover, the reported incorporati on 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. (C) 1999 Elsevier Science B.V. All rights reserved.