Phenotype and functional analysis of human monocytes-derived dendritic cells loaded with a carbosilane dendrimer.
Dendritic cells (DCs) play a major role in development of cell-mediated immunotherapy due to their unique role in linking innate and adaptive immunities. In spite of improvement in this area, strategies employing ex vivo generated DCs have shown limited efficacy in clinical trials. Dendrimers have been proposed as new carriers for drug delivery in aim to ameliorate DCs antigen loading that is a pivotal point in DCs approaches. In this study, we have investigated the phenotypic and functional characteristics of human monocytes-derived dendritic cells after HIV-derived peptides uptake in vitro. We have found that iDCs and mDCs were able to capture efficiently water soluble carbosilane (CBS) dendrimer 2 G-NN16 and did not induce changes in maturation markers levels at the DCs surface. Therefore, CBS 2 G-NN16-loaded mDCs migrated as efficiently as unloaded DCs towards CCL19 or CCL21. Furthermore, DCs viability, activation of allogenic naïve CD4 + T cells by mDCs and secretion of cytokines were not significantly changed by 2 G-NN16 loading. Summing up, our data indicate that CBS 2 G-NN16 has no negative effects on the pivotal properties of DCs in vitro. It should therefore be feasible to further develop this antigen loading strategy for clinical use in immunotherapy against viral infections.
Pion
Marjorie
M
Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain.
Serramia
Maria J
MJ
Diaz
Laura
L
Bryszewska
Maria
M
Gallart
Teresa
T
García
Felipe
F
Gómez
Rafael
R
de la Mata
Francisco J
FJ
Muñoz-Fernandez
Maria Á
MÁ
D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D050091:Dendrimers / Q000494:pharmacology* / Q000633:toxicity; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000166:cytology*; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D012821:Silanes / Q000494:pharmacology* / Q000633:toxicity
D015415:Biomarkers; D016207:Cytokines; D050091:Dendrimers; D010455:Peptides; D012821:Silanes; C504072:carbosilane