A monoclonal antibody specific for mouse dendritic cells.

Nussenzweig, Michel C.; Steinman, Ralph M.; Witmer, Margit D.; Gutchinov, Badma

doi:10.1073/pnas.79.1.161

Cited by 224 publications

(134 citation statements)

References 14 publications

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“…6a I-II). 33D1 is a marker of mature DC [38]. MSC/IFN-β/GFP-treated mice had significantly more mature splenic DCs than MSC/GFP-treated mice (P<0.01).…”

Section: Ifn-β Inactivatesmentioning

confidence: 95%

Mesenchymal Stem Cells Overexpressing IFN-β Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model

Ling

Marini

Konopleva

et al. 2010

Cancer Microenvironment

111

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We previously demonstrated that mesenchymal stem/stromal cells (MSC) are recruited to tumors and that IFN-β produced by MSC inhibited tumor growth in xenograft models. Because of a deficient immune system, murine xenograft models cannot fully recapitulate tumor and immune cell interactions during progression. Therefore we investigated the capacity of MSC to migrate to and engraft into primary breast tumor sites and subsequently explore mechanisms of tumor inhibition by MSC-delivered IFN-β in a syngeneic, immunocompetent murine model. Herein we report that 1) systemically administrated MSC migrate to established 4 T1 breast cancer sites and localize among the tumor-stroma border and throughout the tumor mass; 2) high levels of IFN-β secreted by MSC are detectable in the tumor microenvironment but not in circulation; 3) intratumorally produced IFN-β inactivates constitutive phosphorylation of signal transducer activator transcription factor 3 (Stat3), Src, and Akt and down-regulates cMyc and MMP2 expression in 4 T1 cells, and 4) in mice with established breast cancer IFN-β expressing MSC administered systemically resulted in inhibition of primary cancer growth and in dramatic reduction of pulmonary and hepatic metastases. 5) MSC-IFN-β treated, but not control mice, maintained normal levels of splenic mature dendritic (DC), CD8+ T cells and CD4+/Foxp3+ regulatory T-cells (Treg). Our findings suggest that MSC are capable of migrating to tumor sites in an immunocompetent environment, that IFN-β produced by MSC suppresses breast cancer growth through inhibition of Stat3 signaling, and dramatically reduces pulmonary and hepatic metastases.

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“…6a I-II). 33D1 is a marker of mature DC [38]. MSC/IFN-β/GFP-treated mice had significantly more mature splenic DCs than MSC/GFP-treated mice (P<0.01).…”

Section: Ifn-β Inactivatesmentioning

confidence: 95%

Mesenchymal Stem Cells Overexpressing IFN-β Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model

Ling

Marini

Konopleva

et al. 2010

Cancer Microenvironment

111

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“…When the 33D1 mAb was developed by Michel Nussenzweig in 1982 [16], selective removal of the tiny fraction of DC became feasible. The absence of DC ablated much of the MLR stimulating activity from the total suspension of spleen cells [17].…”

Section: Dendritic Cells As Immunogens For Transplantation Reactionsmentioning

confidence: 99%

“…Instead, we and others used the distinct morphology of DC to identify, enrich and begin to characterize these cells in several tissues and species, and to prepare the first monoclonals, i.e. 33D1, now anti-DCIR2 [16][17][18] and N418 anti-CD11c [19,20]. The distinct morphology that we used to guide our preparation of DC has now been observed in living lymph nodes, where each DC continually probes its environment by extending and retracting processes [21].…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells: Understanding immunogenicity

2007

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The impetus for the discovery of dendritic cells in 1972 was to understand immunogenicity, the capacity of an antigenic substance to provoke immunity. During experiments to characterize "accessory" cells that enhanced immunity, we spotted unusual stellate cells in mouse spleen. They had a distinct capacity to form and retract processes or dendrites and were named dendritic cells (DC). DC proved to be different from other cell types and to be peculiarly immunogenic when loaded with antigens. When Langerhans cells were studied, immunogenicity was found to involve two steps: antigen presentation by immature DC and maturation to elicit immunity. Antigenbearing DC were also immunogenic in vivo and were therefore termed "nature's adjuvants". Several labs then learned to generate large numbers of DC from progenitors, which accelerated DC research. Tolerogenicity via DC, including the control of foxp3 + suppressor T cells, was recently discovered. Two areas of current research that I find intriguing are to identify mechanisms for antigen uptake and processing, and for the control of different types of immunity and tolerance. These subjects should be studied in vivo with clinically relevant antigens, so that the activities of DC can be better integrated into the prevention and treatment of disease in patients.

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“…To examine the capacity of different receptors to immunize scarce microbial-specific T cells in the polyclonal repertoire, as contrasted with a prior study on presentation to OVA-specific TCR transgenic T cells using α-Langerin, α-DEC205, and α-DCIR2 (31), we genetically engineered mAbs against Langerin (L31) (33), DCIR2 (33D1) (35), DEC205 (NLDC145) (36,37), and a nonreactive control Ig (GL117) (38) to express HIV gag-p24. We also cloned and engineered an antibody against the more recently described receptor Clec9A to express HIV gag-p24 (10B4) (28).…”

mentioning

confidence: 99%

Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A

Idoyaga

Lubkin

Fiorese

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

254

273

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Improved protein-based vaccines should facilitate the goal of effective vaccines against HIV and other pathogens. With respect to T cells, the efficiency of immunization, or "immunogenicity," is improved by targeting vaccine proteins to maturing dendritic cells (DCs) within mAbs to DC receptors. Here, we compared the capacity of Langerin/CD207, DEC205/CD205, and Clec9A receptors, each expressed on the CD8 + DC subset in mice, to bring about immunization of microbial-specific T cells from the polyclonal repertoire, using HIV gag-p24 protein as an antigen. α-Langerin mAb targeted splenic CD8 + DCs selectively in vivo, whereas α-DEC205 and α-Clec9A mAbs targeted additional cell types. When the mAb heavy chains were engineered to express gag-p24, the α-Langerin, α-DEC205, and α-Clec9A fusion mAbs given along with a maturation stimulus induced comparable levels of gag-specific T helper 1 (Th1) and CD8 + T cells in BALB/c × C57BL/6 F1 mice. These immune T cells were more numerous than targeting the CD8 − DC subset with α-DCIR2-gag-p24. In an in vivo assay in which gag-primed T cells were used to report the early stages of T-cell responses, α-Langerin, α-DEC205, and α-Clec9A also mediated cross-presentation to primed CD8 + T cells if, in parallel to antigen uptake, the DCs were stimulated with α-CD40. α-Langerin, α-DEC205, and α-Clec9A targeting greatly enhanced T-cell immunization relative to nonbinding control mAb or nontargeted HIV gag-p24 protein. Therefore, when the appropriate subset of DCs is targeted with a vaccine protein, several different receptors expressed by that subset are able to initiate combined Th1 and CD8 + immunity.antigen presentation | C-type lectins | cross-priming A major goal in the development of effective vaccines against pathogens such as HIV and malaria is the induction of durable and protective T-cell immunity. Attenuated viral vectors are being emphasized widely as a vaccine platform to elicit T-cell immunity in humans (1). Attenuated vectors have potential limitations with respect to immunogenicity and repeated use, however (2). Protein vaccines could provide a stand-alone or complementary platform (e.g., to viral vectors), with relative ease of production and ability to be repeatedly injected. Proteins are poorly immunogenic for T cells, however, even when administered repeatedly in high doses.Recent progress in immunobiology provides the potential to overcome this obstacle. The immunogenicity of proteins can be greatly enhanced by improving the delivery of protein to dendritic cells (DCs). To do this, one approach is to introduce the protein into mAbs that efficiently and specifically target to DC receptors in situ, within lymphoid tissues, and then to coadminister the fusion antibody with an appropriate agonist for DC maturation [reviewed in (3, 4)]. Delivery of vaccine proteins within mAbs increases the efficiency of antigen presentation on MHC class I and II molecules ∼100-fold and allows protein vaccines to induce T helper 1 (Th1) type CD4 + T cells and CD8 + T cells (5-8).The DC ...

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A monoclonal antibody specific for mouse dendritic cells.

Cited by 224 publications

References 14 publications

Mesenchymal Stem Cells Overexpressing IFN-β Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model

Mesenchymal Stem Cells Overexpressing IFN-β Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model

Dendritic cells: Understanding immunogenicity

Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A

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