Enhanced delivery of immunoliposomes to human dendritic cells by targeting the multilectin receptor DEC-205

Dendritic cells (DC) are specialized white blood cells that initiate and direct immune responses. Targeting DC surface proteins to deliver liposomes carrying antigens has demonstrated potential for eliciting antigen -specific immune responses. To evaluate this strategy in preclinical studies, we prepared anti-human DEC-205 immunoliposomes (anti-hDEC-205 iLPSM) and compared their uptake by monocyte-derived DC (MoDC) and blood DC (BDC) with conventional liposomes (cLPSM). Antibody conjugation increased the number of immature MoDC taking up liposornes to 70-80%, regardless of the antibody coupled, whereas less than 20% endocytosed cLPSM. Anti -hDEC- 205 -IgG specifically increased cell uptake by 15% and the total iLPSM uptake six-fold. The non-specific iLPSM uptake was unlikely to be Fc receptor-mediated as excess immunoglobulins failed to block the uptake. Only a small population (7-24%) of mature MoDC took up cLPSM and control iLPSM. In contrast, similar to 70% of mature MoDC took up anti-hDEC-205 iLPSM, endocytosing 10-fold more iLPSM than the control iLPSM. Anti-hDEC-205 iLPSM uptake by CD1c(+) BDC was similar to the immature MoDC, but was five-fold increased compared to the control iLPSM. Confocal microscopy confirmed that the anti-hDEC-205 iLPSM were phagocytosed by DC and available for antigen processing. Thus, DEC-205 is an effective target for delivering liposomes to human DC. (c) 2007 Elsevier Ltd. All rights reserved