CliniMACS® CD304 (BDCA-4) Product Line

In human blood and bone marrow, CD304 (BDCA-4, Neuropilin-1) is exclusively expressed on plasmacytoid dendritic cells (PDCs), which are characterized as CD11c, CD123bright, and CD303 (BDCA-2)
+
.
1,2
PDCs represent about 0.2% of white blood cells.
They are the main producers of type 1 interferons, which strongly stimulate the differentiation of other immune cells. PDCs have a poor pino- and phagocytosis capacity and take up exogenous antigens predominantly by receptor-mediated endocytosis.
3
Apart from their immune stimulatory functions, they are also intensively discussed to be involved in tolerance induction.
4
The CliniMACS® CD304 (BDCA-4)

Data and images for
CliniMACS
®
CD304 (BDCA-4) Product Line

Figures

Figure 1

Flow cytometric analysis of CD304 (BDCA-4)–enriched cells from leukapheresis harvest using the CliniMACS CD304 (BDCA-4) System.
Before enrichment
After enrichment
View details

Figure 1

Flow cytometric analysis of CD304 (BDCA-4)–enriched cells from leukapheresis harvest using the CliniMACS CD304 (BDCA-4) System.
View details

Figure 1

Flow cytometric analysis of CD304 (BDCA-4)–enriched cells from leukapheresis harvest using the CliniMACS CD304 (BDCA-4) System.

Specifications for
CliniMACS
®
CD304 (BDCA-4) Product Line

Overview

In human blood and bone marrow, CD304 (BDCA-4, Neuropilin-1) is exclusively expressed on plasmacytoid dendritic cells (PDCs), which are characterized as CD11c, CD123bright, and CD303 (BDCA-2)
+
.
1,2
PDCs represent about 0.2% of white blood cells.
They are the main producers of type 1 interferons, which strongly stimulate the differentiation of other immune cells. PDCs have a poor pino- and phagocytosis capacity and take up exogenous antigens predominantly by receptor-mediated endocytosis.
3
Apart from their immune stimulatory functions, they are also intensively discussed to be involved in tolerance induction.
4
The CliniMACS® CD304 (BDCA-4) Product Line consists of murine CD304 (BDCA-4) monoclonal antibodies conjugated to superparamagnetic iron dextran particles.
One vial contains 7.5 mL sterile, non-pyrogenic solution.
The performance of the CliniMACS CD304 (BDCA-4) Product Line depends on the individual separation strategy. For information on respective capacities, refer to the CliniMACS User Manual or contact your local representative.
Please inquire about required CliniMACS System components and accessories.

Detailed product information

Applications

The CliniMACS CD304 (BDCA-4) Product Line was developed for enrichment of CD304 (BDCA-4)
+
plasmacytoid dendritic cells from human heterogeneous hematologic cell populations in combination with the CliniMACS System.

Referenced literature

The therapeutic potential of PDCs has been studied in several mouse models, investigating, for example, their regulatory role in tumor regression
5,6
or induction of allograft tolerance
7
. Pre-clinical studies in humans, for example, analyze impaired PDC function within tumor environment
8
or their immunosuppressive role in GvHD
9
.

Disclaimer

The CliniMACS
®
System components, including Reagents, Tubing Sets, Instruments, and PBS/EDTA Buffer, are designed, manufactured and tested under a quality system certified to ISO 13485.
In the EU, the CliniMACS System components are available as CE-marked medical devices for their respective intended use, unless otherwise stated. The CliniMACS Reagents and Biotin Conjugates are intended for
in vitro
use only and are not designated for therapeutic use or direct infusion into patients. The CliniMACS Reagents in combination with the CliniMACS System are intended to separate human cells. Miltenyi Biotec as the manufacturer of the CliniMACS System does not give any recommendations regarding the use of separated cells for therapeutic purposes and does not make any claims regarding a clinical benefit. For the manufacturing and use of target cells in humans the national legislation and regulations - e.g., for the EU the Directive 2004/23/EC ("human tissues and cells"), or the Directive 2002/98/EC ("human blood and blood components") - must be followed. Thus, any clinical application of the target cells is exclusively within the responsibility of the user of a CliniMACS System.
In the US, the CliniMACS CD34 Reagent System, including the CliniMACS Plus Instrument, CliniMACS CD34 Reagent, CliniMACS Tubing Sets TS and LS, and the CliniMACS PBS/EDTA Buffer, is FDA approved as a Humanitarian Use Device (HUD), authorized by U.S. Federal law for use in the treatment of patients with acute myeloid leukemia (AML) in first complete remission. The effectiveness of the device for this indication has not been demonstrated. Other products of the CliniMACS Product Line are available for use only under an approved Investigational New Drug (IND) application, Investigational Device Exemption (IDE) or FDA approval.
CliniMACS GMP MicroBeads are for
ex vivo
cell processing only.
CliniMACS MicroBeads are for research use only and not for human therapeutic or diagnostic use.

Resources for
CliniMACS
®
CD304 (BDCA-4) Product Line

Documents and Protocols

Brochures/posters

Manufacturing dendritic cell products for clinical research

Certificates

Please follow this
link
to search for Certificates of Analysis (CoA) by lot number.

References for
CliniMACS
®
CD304 (BDCA-4) Product Line

Publications

  1. Dzionek, A. et al. (2000) BDCA-2, BDCA-3, BDCA-4: Three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol 165: 6037-6046
  2. Dzionek, A. et al. (2002) Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions. Hum. Immunol. 63: 1133-1148
  3. Benitez-Ribas, D. et al. (2006)
    Plasmacytoid dendritic cells of melanoma patients present exogenous proteins to CD4
    +
    T cells after Fc gamma RII-mediated uptake.
    J. Exp. Med. 203: 1629-1635
  4. Moseman, E. A. et al. (2004) Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. J Immunol 173: 4433-4442
  5. Heckelmiller, K. et al. (2002) Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy. Eur. J. Immunol. 32: 3235-3245
  6. Liu, C. et al. (2008) Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J. Clin. Invest. 118: 1165-1175
  7. Orchando, J. C. et al. (2006) Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat Immunol 7: 652-62
  8. Hartmann, E. et al. (2003) Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res. 63: 6478-6487
  9. Hadeiba, H. et al. (2008) CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease. Nat Immunol 9: 1253-1260
  10. de Vries et al. (2010) 11th Int. Sym. Dendritic Cells : S05-003

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