Activation and inhibition of the immune system

A method of treating an autoimmune disease comprising administering a pharmaceutically-effective dose of an NF-κB inhibitor to induce an anergic response in a mammal wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

A method of treating an allergy in a mammal, such as a human, comprising administering a pharmaceutically-effective dose of an NF-κB inhibitor to induce an anergic response in a mammal wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

A method of preventing transplant rejection in a mammal, such as a human, comprising administering a pharmaceutically-effective dose of an NF-κB inhibitor to induce an anergic response in a mammal wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

A method, according to any one of the preceding claims comprising administering a vector comprising nucleic acid encoding an NF-κB inhibitor operatively linked to regulatory elements necessary for expression of said nucleic acid.

NF-κB inhibitor for use in inducing an anergic response or inhibiting antigen presentation in a mammal.

NF-κB inhibitor for use in treating autoimmune disease or allergy by inducing an anergic response wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

NF-κB inhibitor for use to inhibit the rejection of transplanted tissue by inducing an anergic response wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

Use of NF-κB inhibitor in the manufacture of a medicament to induce an anergic response.

A method or inhibitor according to any preceding claim wherein the inhibitor is IκBα or PSI or an IKK2 dominant negative mutant.

A method or an inhibitor according to any preceding claim, wherein the inhibitor is encoded by nucleic acid in a vector, the vector additionally comprising regulatory elements operatively linked to said nucleic acid.

A method of stimulating antigen presentation or of stimulating an immune response in a mammal, such as a human, comprising administering a pharmaceutically effective amount of an NF-κB inducer wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

An NF-κB inducer for use to stimulate an immune response in a mammal, such as a human, wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

An NF-κB inducer for use in the manufacture of a medicament to treat infectious disease or cancer or a condition characterised by aberrant types or aberrantly high levels of harmful molecules in the body wherein the mammal, such as a human, is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

A method of inhibiting the maturation and activation of APCs, such as dendritic cells in vivo or in vitro, comprising administering an effective amount of an inhibitor of NF-κB.

A method of stimulating the maturation and activation of APCs, such as dendritic cells in vivo or in vitro, comprising administering an effective amount of an inducer of NF-κB.

The method, inhibitor, inducer or use of any of the preceding claims wherein the inhibitor or inducer is targeted to APCs such as dendritic cells or precursors thereof.

The method, inhibitor, inducer or use of any of the preceding claims wherein APCs, such as dendritic cells or precursors thereof are exposed to the inhibitor or inducer in vitro and introduced into the mammal.

A polynucleotide encoding an antigenic molecule and an NF-κB inhibitor.

A polynucleotide encoding an antigenic molecule and an NF-κB inducer.

A kit of parts or composition or a chimaeric molecule, comprising (1) a modulating portion comprising or encoding a NF-κB inhibitor or inducer and (2) an antigenic portion comprising or encoding an antigenic molecule.

The method, inhibitor, inducer, use, polynucleotide, kit of parts, composition or chimaeric molecule of any one of the preceding claims wherein the antigenic molecule comprises an epitope present on transformed or cancerous cells or on a pathogenic organism, or on a cell infected by a pathogenic organism, or a polypeptide expressed in a pathologic condition such as Alzheimer's disease or a spongiform encephalopathy.

A vaccine effective against cancer, or cancer or tumour cells, or against a pathogenic organism or cell infected with a pathogenic organism, or a disease characterised by the expression of a polypeptide in a pathologic condition such as Alzheimer's disease or a spongiform encephalopathy comprising an effective amount of an NF-κB inducer or polynucleotide encoding an NF-κB inducer, further comprising an antigen or polynucleotide encoding an antigen, having an epitope present on the cancer or tumour cells, or the pathogenic organism or cell infected with a pathogenic organism or present in a polypeptide associated with a pathologic condition.

A method of killing target cells in a patient which target cells aberrantly express a first epitope, the method comprising the steps of (1) obtaining APCs, such as dendritic cells, from said patient;

• (2) contacting said APCs, such as dendritic cells, with a NF-κB inducer ex vivo;
• (3) optionally contacting said cells with the said epitope or with a polynucleotide or expression vector encoding the said epitope and (4) reintroducing the so treated APCs, such as dendritic cells, into the patient.

Use of an inhibitor of NF-κB or nucleic acid encoding an inhibitor of NF-κB in the manufacture of a medicament for treatment of a patient in need of inhibition of the maturation and activation of APCs, such as dendritic cells wherein the patient is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.

Use of an inducer of NF-KB in the manufacture of a medicament for treatment of a patient in need of stimulation of the maturation and activation of APCs, such as dendritic cells wherein the patient is administered an antigenic molecule or polynucleotide encoding an antigenic molecule.