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US 6,218,371 B1Granted
Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines
AssigneeUniversity of Iowa Research Foundation
InventorsArthur M. Krieg, George Weiner
Life of this patent
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Abstract
The present invention relates to synergistic combinations of immunostimulatory CpG oligonucleotides and immunopotentiating cytokines. In particular, the invention relates to methods of stimulating an immune response using the synergistic combination of compounds and products related thereto.
Claims23
A method for stimulating an immune response in a subject, comprising:
- administering to a subject exposed to an antigen an effective amount for inducing a synergistic antigen specific immune response of an immunopotentiating cytokine selected from the group consisting of GM-CSF, IL-2, IL-4 and IFN-γ, and an immunostimulatory CpG oligonucleotide having a sequence including at least the following formula:
- 5′ X1CGX2 3′
- wherein the oligonucleotide includes at least 8 nucleotides wherein C is unmethylated and wherein X1 and X2 are nucleotides, wherein the cytokine is a peptide, whereby an antigen is optionally additionally administered, and wherein the antigen and the CpG oligonucleotide are not conjugated.
A composition, comprising:
- an effective amount for synergistically activating a dendritic cell of an immunostimulatory CpG oligonucleotide having a sequence including at least the following formula:
- 5′ X1CGX2 3′
- wherein the oligonucleotide includes at least 8 nucleotides wherein C is unmethylated and wherein X1 and X2 are nucleotides;
- and a cytokine selected from the group consisting of GM-CSF, IL-2, IL-4 and IFN-γ, wherein the cytokine is a peptide.
1 more element
A method for activating a dendritic cell, comprising:
- contacting a dendritic cell exposed to an antigen with an effective amount for synergistically activating a dendritic cell of an immunopotentiating cytokine selected from the group consisting of GM-CSF, IL-2, IL-4 and IFN-γ, and an immunostimulatory CpG oligonucleotide having a sequence including at least the following formula:
- 5′ X1CGX2 3′
- wherein the oligonucleotide includes at least 8 nucleotides wherein C is unmethylated and wherein X1 and X2 are nucleotides, wherein the cytokine is a peptide, whereby an antigen is optionally additionally administered, and wherein the antigen and the CpG oligonucleotide are not conjugated.
A method for treating a subject having a neoplastic disorder, comprising:
- administering to the tumor of a subject having a neoplastic disorder an immunopotentiating cytokine selected from the group consisting of GM-CSF, IL-2, IL-4 and IFN-γ, and an immunostimulatory CpG oligonucleotide having a sequence including at least the following formula:
- 5′ X1CGX2 3′
- wherein the oligonucleotide includes at least 8 nucleotides wherein C is unmethylated and wherein X1 and X2 are nucleotides, in an amount effective for synergistically increasing survival time of the subject with respect to a subject administered the immunostimulatory CpG oligonucleotide or the immunopotentiating cytokine alone, where the cytokine is a peptide.
Dependencies are inferred from the claim text.