Transduction of dendritic cells with adenoviral vectors encoding CTLA4-Ig markedly reduces their allostimulatory activity

Лу, Л.; Lee, W. C.; Gambotto, Andrea; Zhong, Cuiping; Robbins, Paul D.; Shen, Qian; Fung, John J.; Thomson, Angus W.

doi:10.1016/s0041-1345(98)01774-6

Cited by 12 publications

(6 citation statements)

References 3 publications

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“…Other gene therapy strategies aimed at modifying host islet autoimmunity include the introduction of cytokine genes such as IL-10 (53-58), IL-4 (59-63), TGF-β (64), and IFN-γ receptor (65,66), and blockade of costimulatory molecules (67,68). Promising results have been obtained in animal models; however, all of these strategies are geared toward downregulation of existing autoimmune T cells.…”

Section: Figurementioning

confidence: 99%

Prevention of type 1 diabetes by gene therapy

Tian¹,

Bagley²,

Crétin³

et al. 2004

J. Clin. Invest.

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The autoimmune disease type 1 diabetes in humans and NOD mice is determined by multiple genetic factors, among the strongest of which is the inheritance of diabetes-permissive MHC class II alleles associated with susceptibility to disease. Here we examined whether expression of MHC class II alleles associated with resistance to disease could be used to prevent the occurrence of diabetes. Expression of diabetes-resistant MHC class II I-Aβ chain molecules in NOD mice following retroviral transduction of autologous bone marrow hematopoietic stem cells prevented the development of autoreactive T cells by intrathymic deletion and protected the mice from the development of insulitis and diabetes. These data suggest that type 1 diabetes could be prevented in individuals expressing MHC alleles associated with susceptibility to disease by restoration of protective MHC class II expression through genetic engineering of hematopoietic stem cells

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Section: Figurementioning

confidence: 99%

Prevention of type 1 diabetes by gene therapy

Tian¹,

Bagley²,

Crétin³

et al. 2004

J. Clin. Invest.

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“…So modified DCs have also shown high stimulatory activity in both allogeneic and autologous mixed lymphocyte reaction (MLR). These data have also supported the efficiency of the recombinant viral vectors in studies on the biology of DCs, including the expression of specific antigens for active immune therapy (Aicher et al, 1997;Dietz and Vuk-Pavlović, 1998;Lu et al, 1998).…”

Section: Development Of Novel Therapeutic Strategies With Dendritic Cmentioning

confidence: 82%

“…In investigation on the in vivo-properties of the so modified DCs, skin transplantation of humanized immunodeficient non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, engrafted with human skin, reconstituted via intra-peritoneal injection with allogeneic mononuclear cells (MNCs) mixed with 1 × 10 6 autologous to the skin donor DCs, transduced with either recombinant virus gene construct AdV/IL-10 or of recombinant viral vector AdV/MX-17, a reduced skin graft rejection, characterized by reduced infiltration with mononuclear cells and less dermo-epidermal junction destruction in comparison with the animals with inoculation of DCs, modified with the control virus alone, has been observed. Transduced by appropriate adenoviral gene constructs, immature DCs have shown the abilities to differentiate in different directions in respective appropriate conditions of cultivation (Addison et al, 1995;Chen et al, 1997;Dietz and Vuk-Pavlović, 1998;Gambotto et al, 1999;Lu et al, 1998). For example, in the presence of monocyte-conditioned medium, they have indicated ability to express the surface markers of mature DCs, such as CD25, CD83, high levels of molecules CD86 and HLA-DR, or to secrete of IL-12.…”

Section: Development Of Novel Therapeutic Strategies With Dendritic Cmentioning

confidence: 99%

Differentiation of stem and progenitor cells from bone marrow in activated dendritic cells and lymphocytes with anti-malignant properties

Sainova¹

2013

Afr. J. Pharm. Pharmacol.

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Dendritic cells (DCs) have been characterized as powerful antigen-presenting cells (APCs), which possess the abilities for immune modulation and are used in composition of anti-malignant vaccines and gene-engineered products. By appropriate cultivation, modifications of DCs have shown abilities for an enhanced expression of specific effector molecules. Studies on their biology are focused on their role as main immune response modulators. These properties characterize them as promising candidates for construction of novel safe vaccines and gene-engineered products. In this direction, attention is directed to development of methods and techniques for transduction of in vitro-and/or ex vivo-cultivated DCs with previously designed recombinant viral vectors with inserted genes, coding respective malignant antigens. Studies on the biology of lymphocytes are mainly focused on their role in cellular and humoral immune response. Their cultivation and differentiation in the presence of appropriate antigens, on one hand, and by appropriate modifications, on the other hand, have shown the abilities for an enhanced expression of specific effective molecules. These properties have characterized them as promising candidates for construction of novel safe vaccines and geneengineering products.

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“…Nevertheless, the adenoviral vectors used to efficiently deliver the transgenes simultaneously activate the DCs. Thus, transgene expression is overcome by the vigorous up-regulation of costimulatory molecules on the DC surface (14,15). It seems to be crucial to explore novel approaches to modify DC allostimulatory activity.…”

Section: Discussionmentioning

confidence: 99%