Compositions and methods for modulating immune responses

A technology of immune response and composition, applied in the direction of drug combination, pharmaceutical formula, allergen antigen components, etc., can solve the problem of lack of support and usefulness

Active Publication Date: 2010-02-10
THE UNIV OF QUEENSLAND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, to the best of the inventors' knowledge, there is no clinical evidence supporting the usefulness of this strategy
[0042] Surprisingly, it was found that co-administration of an NF-κB inhibitor and an antigen (both in soluble form at the same time, or one in soluble form and the other encapsulated in liposomes) in vivo was significantly more effective in producing response to the antigen. Ineffective in tolerogenic response

Method used

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  • Compositions and methods for modulating immune responses
  • Compositions and methods for modulating immune responses
  • Compositions and methods for modulating immune responses

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0097]Methods that have been developed to prepare microspheres for the delivery of coated agents are described in the literature, eg, as Doubrow, M., Ed., "Microcapsules and Nanoparticles in Medicine and Pharmacy," CRCPress, Boca Raton, 1992. The description of the method is also found in Mathiowitz and Langer (1987, J.Controlled Release 5, 13-22); Mathiowitz et al. (1987, Reactive Polymers 6, 275-283); and Mathiowitz et al. (1988, J.Appl . Polymer Sci.35, 755-774) and US Patent No. 5,213,812, US Patent No. 5,417,986, US Patent No. 5,360,610 and US Patent No. 5,384,133. The choice of method depends on the choice of polymer, size, shape and desired crystallinity, as described (e.g. Mathiowitz et al. (1990, Scanning Microscopy 4:329-340; 1992, J. Appl. Polymer Sci. .45, 125-134); and Benita et al. (1984, J. Pharm. Sci. 73, 1721-1724)).

[0098] In solvent evaporation, the polymer is dissolved in a volatile organic solvent, such as dichloromethane, as described, for example, in ...

Embodiment 1

[0235] Antigen-specific inhibition of arthritis by liposomes

[0236] Materials and methods

[0237] Reagent

[0238] Fluorescein isothiocyanate (FITC), ovalbumin (OVA), methylated bovine serum albumin (mBSA) were purchased from Sigma-Aldrich (Missouri, USA). Penicillin, streptomycin, L-glutamine, sodium pyruvate and 2-mercaptoethanol were purchased from Invitrogen (California, USA). Complete Freund's adjuvant (CFA) was obtained from Sigma-Aldrich (Missouri, USA). Carboxyfluorescein diacetate succinimidyl ester (CFSE) was obtained from Molecular Probes (Oregon, USA). Phycoerythrin (PE)-labeled KJ1-26 antibody was purchased from BD Pharmingen (California, USA). Anti-mouse MHC II-FITC was purchased from Biolegend (California, USA). The CD4 epitope of OVA (sequence 323-339) was obtained from Auspep (Victoria, Australia). All other reagents were at least of analytical grade.

[0239] mouse

[0240] Male C57 / B16 and BALB / c mice were obtained from ARC, an OVA-specifi...

Embodiment 2

[0326] Antigen-associated liposomes or antigen-associated microspheres induce antigen-specific suppression by inducing regulatory T cells

[0327] Materials and methods

[0328] Reagent

[0329] Poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres were prepared by combining ovalbumin, curcumin, PLGA and polyvinyl alcohol (PVA), then mixing at 13500 rpm, followed by stirring at 800 rpm. After density centrifugation, the particles were dispersed in a 5% w / v sucrose solution, sized and lyophilized. Particles were reconstituted in PBS before use. OVA-curcumin liposomes were prepared as described in Example 1.

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Abstract

This invention discloses methods and compositions for modulating immune responses, which involve particulate delivery of agents to immune cells, wherein the agents comprise an inhibitor of the NF-kappa B signaling pathway and an antigen that corresponds to a target antigen. The methods and compositions of the present invention are particularly useful in the treatment or prophylaxis of an undesirable immune response associated with the target antigen, including autoimmune diseases, allergies and transplantation associated diseases.

Description

technical field [0001] The present invention generally relates to compositions and methods for modulating an immune response. More specifically, the present invention relates to the delivery of an agent to immune cells via particles, wherein the agent comprises an inhibitor of the NF-κB signaling pathway and an antigen corresponding to the target antigen. The methods and compositions of the invention are particularly useful for treating or preventing unwanted immune responses (including autoimmune diseases, allergies, and transplant-related diseases) associated with target antigens. Background technique [0002] NF-κB transduces signals from the cell surface to the nucleus. Activation of NF-κB and MAP kinase signal transduction through cell surface receptors via adapter molecules is important for the survival and activation of all cells in the body, including those regulating innate and adaptive immunity, including antigen presentation cells such as dendritic cells (DC). ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K39/35A61K39/00A61K9/127A61P37/04A61P37/00A61P37/06A61P37/02
Inventor R·托马斯N·M·戴维斯B·J·奥沙利文
Owner THE UNIV OF QUEENSLAND
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