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Activation and inhibition of the immune system

An inhibitor, encoded technology, applied in the field of activation and suppression of the immune system, can solve the problem that activation is not beneficial

Inactive Publication Date: 2006-08-16
MATHILDA & TERENCE KENNEDY INST OF RHEUMATOLOGY TRUST
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This was unexpected since NF-κB has been shown to be activated in DC (Feuillard et al. (1996) Eui. J Immunol 26:2547-2551; Granelli-Piperno et al. (1995) Proc Natl. Acad. Sci. USA 92, 10944-10948), so further activation would not have been expected to be beneficial

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  • Activation and inhibition of the immune system
  • Activation and inhibition of the immune system
  • Activation and inhibition of the immune system

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Experimental program
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Embodiment Construction

[0199] Materials and methods

[0200] 1. Reagents

[0201] Human recombinant GM-CSF and TNFα were kindly provided by Dr. Glenn Larsen (GI) and Dr. D Tracey (BASF), respectively. Human recombinant IL-4 was purchased from R&D System (Minneapolis, USA). PMA, LPS and ionomycin were obtained from Sigma Chemical Co. (St Louis, USA). Proteosome inhibitor Cbz-Ile-Glu (O-tert-butyl-Ala-cerema (PSI) was obtained from Calbiochem (Nottingham, UK). M-CSF was obtained from Genetics Institute (Boston, USA).

[0202] 2. Preparation of Peripheral Blood Mononuclear Cells

[0203] Peripheral blood mononuclear cells (PBMC) were obtained by density centrifugation of leukopheresis residues obtained from healthy volunteers (North London Blood Trahsfusion Service, Colindale, UK). The heparinized residue was diluted 2-fold with HBSS, 25 ml was carefully overlaid on an equal volume of Ficoll-Hypaque lymphoprep (Nycomed, Oslo, Norway) in a 50 ml sterile tube, and then centrifuged at 2000 rpm for 30 ...

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Abstract

Induction of an anergic response by NF-ºB inhibitors and the inhibition of immune response by the administration of an inhibitor of NF-ºB is disclosed. Examples ofNF-ºB inhibitors include IºB±, PSI, a nucleotide encoding IºB± anti-sense nucleic acid encoding an NF-ºB sequence, such as RelB, and anti- NF-ºB antibodies. Also disclosed are vectors encoding inducers and inhibitors of NF-ºB, for example adenoviral vectors.

Description

[0001] This application is a divisional application of the following applications: filing date: December 22, 2000; application number: 00819105.0 (PCT / GB00 / 04925); invention title: "activation and suppression of the immune system". field of invention [0002] The present invention relates to the use of inducers and inhibitors of NF-κB to activate and suppress the immune system, and the use of the inducers and inhibitors to treat transplant rejection, autoimmune diseases, allergies, infectious diseases and cancers. Background technique [0003] Antigen presentation is a key step in initiating an immune response, and dendritic cells (DCs) are considered to be the most effective antigen-presenting cells for naive T cells. This is partly due to their high expression of MHC and co-stimulatory molecules (Hart (1997) Blood 90, 3245-3287). However, little is known about the biochemical pathways that regulate the function of antigen presentation, partly due to the difficulty of trans...

Claims

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Application Information

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IPC IPC(8): A61K38/16A61K48/00C12N15/62C07K14/00A61P35/00A61P37/00A61P37/04A61P37/06A61P37/08C12N15/09A61K31/7088A61K35/76A61K38/00A61K38/06A61K38/095A61K38/17A61K38/45A61K39/00A61K39/395A61K45/00A61P25/28A61P31/00A61P37/02C07K14/47C07K16/18C07K19/00
CPCA61K39/0008C12N2799/06A61K39/0011A61K48/00A61K2039/53A61K2039/5154C12N2799/022A61K38/1709A61K38/45A61K38/177A61K38/07A61P25/28A61P31/00A61P35/00A61P37/00A61P37/02A61P37/04A61P37/06A61P37/08A61K39/4622A61K39/464452A61K39/4615
Inventor B·福克斯维尔M·菲尔德曼
Owner MATHILDA & TERENCE KENNEDY INST OF RHEUMATOLOGY TRUST
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