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Title: Enhanced delivery of immunoliposomes to human dendritic cells by targeting the multilectin receptor DEC-205. Author: Badiee A, Davies N, McDonald K, Radford K, Michiue H, Hart D, Kato M. Journal: Vaccine; 2007 Jun 15; 25(25):4757-66. PubMed ID: 17512099. Abstract: 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 liposomes 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, approximately 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.[Abstract] [Full Text] [Related] [New Search]