Fast Monocyte-Derived Dendritic Cell-Based Immunotherapy

Ramadan, Gamal

doi:10.1007/978-1-4939-0345-0_12

Cited by 4 publications

(15 citation statements)

References 17 publications

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“…The HLA-A*0201-restricted peptide ELAGIGILTV (derived from the melanoma-associated differentiation antigen Melan-A/MART-1; A to L substitution at position 2 compared with its natural counterpart for higher immunogenicity and referred to as MART-1 [27][28][29][30][31][32][33][34][35] ), as well as the peptide labeled with a COOH-terminus FITC fluorochrome were produced by the Keck Facility (Yale University).…”

Section: Peptide and Cell Lines Peptidementioning

confidence: 99%

“…The human CD8 + T-cell receptor transgenic cell line DMF5, reactive with both the MART-1 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and MART-1 (27L- 35) epitopes, was kindly provided by John R Wunderlich, Surgery Branch, National Cancer Institute. This line, originally derived from a high avidity tumor-infiltrating lymphocyte clone that mediated tumor regression clinically, has been extensively described previously.…”

Section: Ctl Clonementioning

confidence: 99%

“…synthesis of NPs and Dec-205 ligand coupling to the NP surface PLGA NPs encapsulating MART-1 [27][28][29][30][31][32][33][34][35] peptide (ELAGIG-ILTV) (5 μg peptide/mg PLGA NP) were prepared and functionalized with avidin using a modified o/w emulsion and solvent evaporation-extraction method as described previously. 27 Control NPs (blanks) were synthesized with sterile phosphate-buffered saline replacing the peptide.…”

Section: Ctl Clonementioning

confidence: 99%

“…27 Control NPs (blanks) were synthesized with sterile phosphate-buffered saline replacing the peptide. Fluorescent NPs were formulated by incorporating a FITC-labeled MART-1 [27][28][29][30][31][32][33][34][35] peptide by identical methodologies. Biotinylated anti-human DEC-205 monoclonal antibody or isotype control antibody was added at a concentration of 10 μg/mg PLGA NPs in phosphate-buffered saline and rotated for 40 minutes at room temperature; this antibody concentration was determined to lead to near 100% incorporation on the NP surface as previously described.…”

Section: Ctl Clonementioning

confidence: 99%

“…Among them, the MART-1 (melanoma antigen recognized by T-cells) gene is expressed by normal melanocytes, as well as by a majority of fresh tumor isolates and melanoma cell lines. The MART-1 [27][28][29][30][31][32][33][34][35] peptide (corresponding to residues 27-35 of the non-mutated MART-1 protein) is a well characterized immune-dominant epitope for human leukocyte antigen (HLA)-A2-restricted melanoma-specific CTLs and can be used for the development of immunotherapeutic strategies. 10 Thus far, however, therapeutic benefits associated with DC/ peptide vaccination alone in patients with melanoma have been limited.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen

Saluja¹,

Hanlon²,

Sharp³

et al. 2014

IJN

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Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-1 27–35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for “classical” cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8 + T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency.

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