ICAM3-Fc Outperforms Receptor-Specific Antibodies Targeted Nanoparticles to Dendritic Cells for Cross-Presentation

Abstract

Optimal targeting of nanoparticles (NP) to dendritic cells (DCs) receptors to deliver cancer-specific antigens is key to an efficient induction of anti-tumor 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 mimicking 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.

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

“…For instance, passive drug delivery strategies based on the EPR effect are only applicable to solid tumors above a certain size [ 284 ], whereas active targeting of cell populations provides the possibility of drug delivery to a variety of tumor and non-tumor tissues. Fourth, targeting NPs via surface receptors to myeloid cells has been shown to increase adjuvanticity and immunogenicity in immunotherapy [ 14 , 18 , 285 , 286 ].…”

“…Most NPs are biodegradable and possess low cytotoxicity and low immunogenicity in vitro and in vivo [ 16 ]. In addition, the possibility to link targeting moieties can be utilized for site-specific delivery in vivo [ 17 , 18 ]. For example, the specific targeting of the BLP25 liposome vaccine to tumor cells mainly depends on the presence of an antibody on the liposome surface [ 19 ].…”