Immunostimulatory nucleic acid molecules
AssigneesUniversity of Iowa Research Foundation, Coley Pharmaceutical Group, Inc., The United States of America as represented by the Department of Health and Human Services
InventorsArthur M. Krieg, Joel Kline, Dennis Klinman, Alfred D. Steinberg
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Abstract
Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a Th1 response in a subject are disclosed.
Claims39
A method for ameliorating an immune system deficiency in a subject, comprising the steps of:
- a) contacting lymphocytes obtained from the subject with an antigen and an immunostimulatory nucleic acid, comprising:
- 5′ X1CGX2 3′
- wherein the immunostimulatory nucleic acid includes at least 8 nucleotides and wherein C is unmethylated, wherein X1 and X2 are nucleotides and wherein the immunostimulatory nucleic acid is an immunostimulatory nucleic acid selected from the group consisting of a synthetic immunostimulatory nucleic acid and an immunostimulatory nucleic acid having a phosphate modified backbone ex vivo, thereby producing activated lymphocytes;
- and
- b) readministering the activated lymphocytes obtained in step a) to the subject.
A method for desensitizing a subject against the occurrence of an allergic reaction in response to contact with a particular allergen, comprising administering to the subject an effective amount of an immunostimulatory nucleic acid, comprising:
- 5′ X1CGX2 3′
- wherein the immunostimulatory nucleic acid includes at least 8 nucleotides and wherein C is unmethylated and wherein X1 and X2 are nucleotides and an effective amount of the allergen.
A method of vaccination in a subject, comprising administering to the subject a vaccine antigen or an antigen encoded in a DNA vaccine and immunostimulatory nucleic acid, comprising:
- 5′ X1CGX2 3′
- wherein the immunostimulatory nucleic acid includes at least 8 nucleotides and wherein C is unmethylated and wherein X1 and X2 are nucleotides.
A method for treating leukemia in a subject, comprising administering to the subject an immunostimulatory nucleic acid, comprising:
- 5′ X1CGX2 3′
- wherein the immunostimulatory nucleic acid includes at least 8 nucleotides and wherein C is unmethylated, wherein X1 and X2 are nucleotides, prior to or in conjunction with a chemotherapy, so that the subject's leukemia cells are more sensitive to the chemotherapy.
A composition comprising:
- a plasmid including an immunostimulatory nucleic acid sequence, comprising:
- 5′X1X2CGX3X43′
- wherein C is unmethylated, wherein X1, X2, X3 and X4 are nucleotides and an antigen in a pharmaceutically acceptable carrier.
A composition comprising:
- an isolated immunostimulatory nucleic acid of 8 to 100 nucleotides in length, comprising:
- 5′ X1CGX2 3′
- wherein C is unmethylated, wherein X1 and X2 are nucleotides, and
- an antigen in a pharmaceutically acceptable carrier.
A composition comprising:
- an immunostimulatory nucleic acid comprising:
- 5′ X1CGX2 3′
- wherein the immunostimulatory nucleic acid includes at least 8 nucleotides and wherein C is unmethylated, wherein X1 and X2 are nucleotides, and
- an antigen in a pharmaceutically acceptable carrier.
A composition comprising:
- an immunostimulatory nucleic acid of 8 to 40 nucleotides in length, comprising:
- 5′ X1CGX2 3′
- wherein C is unmethylated, wherein X1 and X2 are nucleotides, and
- an antigen in a pharmaceutically acceptable carrier.
A composition comprising:
- an immunostimulatory nucleic acid, comprising:
- 5′ X1X2CGX3X4 3′
- wherein the immunostimulatory nucleic acid includes at least 8 nucleotides, wherein C is unmethylated, wherein X1, X2, X3 and X4 are nucleotides, and wherein at least one nucleotide has a phosphate backbone modification, and
- an antigen in a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.