Abstract
Optimal targeting of nanoparticles (NP) to dendritic cells (DCs) receptors to deliver cancer-specific antigens is key to the efficient induction of anti-tumour immune responses. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing tètanus toxoid and gp100 melanoma-associated antigen, toll-like receptor adjuvants were targeted to the DC-SIGN receptor in DCs by specific humanized antibodies or by ICAM3-Fc fusion proteins, which acts as the natural ligand. Despite higher binding and uptake efficacy of anti-DC-SIGN antibody-targeted NP vaccines than ICAM3-Fc ligand, no difference were observed in DC activation markers CD80, CD83, CD86 and CCR7 induced. DCs loaded with NP coated with ICAM3-Fc appeared more potent in activating T cells via cross-presentation than antibody-coated NP vaccines. This fact could be very crucial in the design of new cancer vaccines.
Highlights
In the last decade, great effort has been put in developing vaccines targeted to dendritic cells (DCs)
We previously demonstrated that internalization of the receptor when the ligand binds to the carbohydrate recognition domain (CRD) of DC-SIGN is a clathrin-mediated process and once inside the cell they go to late endosomal, LAMP-1 and MHC class II positive, compartments [30,31]
The encapsulation efficiency of peptides and TLR ligands (TLRLs) within the carriers was determined by reverse phase high-performance liquid chromatography
Summary
Great effort has been put in developing vaccines targeted to dendritic cells (DCs). Soluble adjuvants might activate inappropriate (non-antigen presenting) cells resulting in cytokine-related toxicity This is avoided using Ag and adjuvant loading of DCs cultured “in vitro.”. DC based therapies have shown some clinical benefits; DC-based vaccine therapies currently in clinical trials involve the ex vivo culturing of monocyte-derived DCs from the peripheral blood of patients, the loading of tumour-specific antigens and adjuvants, followed by the transfer of the cells back into the patient. This is avoided by using DCs generated ex vivo and Ag and adjuvant loaded “in vitro.”. Blocking Fc receptors by addition of excess IgG hardly affected binding and uptake of NP (about 25%)
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