Immunostimulatory nucleic acid molecules for activating dendritic cells

Abstract

The present invention relates generally to methods and products for activating dendritic cells. In particular, the invention relates to oligonucleotides which have a specific sequence including at least one unmethylated CpG dinucleotide which are useful for activating dendritic cells. The methods are useful for in vitro, ex-vivo, and in vivo methods such as cancer immunotherapeutics, treatment of infectious disease and treatment of allergic disease.

1 .- 39 . (canceled)  
     
     
         40 . A method of treating a tumor in a human or vertebrate animal subject, comprising administering to the subject a nucleic acid delivery complex, said complex comprising a cationic lipid associated with an immunostimulatory nucleic acid 8-80 bases in length comprising at least one unmethylated CpG dinucleotide, in an amount effective to treat the tumor, wherein the administering is in a local region of the tumor.  
     
     
         41 . A method of treating a tumor in a human or vertebrate animal subject, comprising administering to the subject a nucleic acid delivery complex, said complex comprising a cationic lipid associated with an immunostimulatory nucleic acid 8-80 bases in length comprising at least one unmethylated CpG dinucleotide, in an amount effective to treat the tumor, wherein the administering is aerosol administration.  
     
     
         42 . A method of boosting a subject's immune response to a vaccine, wherein the vaccine comprises a cancer antigen, comprising administering to a subject said vaccine and an adjuvant, wherein said adjuvant comprises a cationic lipid associated with an immunostimulatory nucleic acid 8-80 bases in length comprising at least one unmethylated CpG dinucleotide.  
     
     
         43 . A composition for treating a tumor in a human or vertebrate animal subject, consisting essentially of a cationic lipid in association with an immunostimulatory nucleic acid 8-80 bases in length comprising at least one unmethylated cytosine-guanine (CpG) dinucleotide, and optionally, a conventional adjuvant.  
     
     
         44 . A method of generating an anti-tumor cell immune response in a tumor-bearing mammal comprising the step of administering to said mammal a composition comprising a complex, said complex comprising: a cationic lipid and an immunologically active nucleic acid sequence without an expressible cDNA insert, wherein said composition is administered in an amount effective to stimulate an immune response against said tumor.  
     
     
         45 . A method according to  claim 44 , wherein said immunologically active nucleic acid sequence is a bacterially derived plasmid.  
     
     
         46 . A method according to  claim 45 , wherein said bacterially derived plasmid comprises CpG rich motifs.  
     
     
         47 . A method according to  claim 44 , wherein said step of administering is accomplished by intra-tumoral administration or administration into a body cavity compartment containing a tumor.  
     
     
         48 . A method according to  claim 44 , wherein said step of administering is chosen from aerosolization, intravenous injection, intraperitoneal, intranasal, topical, and transmucosal administration.  
     
     
         49 . A method according to  claim 44 , wherein said anti-tumor cell response is a systemic response.  
     
     
         50 . A method of generating a protective anti-tumor cell immune response in a tumor-bearing mammal comprising the step of administering to said mammal a composition comprising a complex, wherein said complex comprises a cationic lipid and an immunologically active nucleic acid sequence that does not encode for an expressible tumor associated antigen, wherein said complex is administered in an amount effective to stimulate an immune response against said tumor.  
     
     
         51 . A method according to  claim 50 , wherein said immunologically active nucleic acid sequence is not capable of transcription or translation of a biologically active peptide in said mammal.  
     
     
         52 . A method according to  claim 50 , wherein said immunologically active nucleic acid sequence is bacterially derived.  
     
     
         53 . A method according to  claim 50 , wherein said immunologically active nucleic acid sequence is a plasmid.  
     
     
         54 . A method according to  claim 50 , wherein said immunologically active nucleic acid sequence comprises genomic bacterial DNA.  
     
     
         55 . A method according to  claim 50 , wherein said immunologically active nucleic acid sequence is a fragment.  
     
     
         56 . A method according to  claim 50 , wherein said immunologically active nucleic acid sequence comprises CpG rich motifs.  
     
     
         57 . A method according to  claim 50 , wherein said step of administering is accomplished by intra-tumoral administration or administration into a body cavity compartment containing a tumor.  
     
     
         58 . A method according to  claim 50 , wherein said step of administering is chosen from aerosolization, intravenous injections, intraperitoneal, intranasal, topical, and transmucosal administration.  
     
     
         59 . A method according to  claim 50 , wherein said protective anti-tumor cell immune response is a systemic response.  
     
     
         60 . A method of increasing the efficacy of a tumor antigen comprising the administration of said tumor antigen and an adjuvant, wherein said adjuvant comprises a cationic molecule:immunologically active nucleic acid sequence complex wherein said immunologically active nucleic acid sequence is without an expressible cDNA insert.  
     
     
         61 . A composition for generating a protective anti-tumor cell immune response in a tumor-bearing mammal consisting essentially of: a cationic lipid; and a immunologically active nucleic acid sequence without an expressible cDNA insert, and optionally, an adjuvant.  
     
     
         62 . A method according to  claim 50 , wherein said nucleic acid sequence is selected from the group comprising plasmid DNA, genomic DNA, messenger RNA, and ribosomal RNA.  
     
     
         63 . A method according to  claim 50 , wherein said immune response comprises immune memory against the tumor.  
     
     
         64 . A method according to  claim 63 , wherein said immune response comprises an adaptive immune response against the tumor.  
     
     
         65 . A method according to  claim 50 , wherein said immune response reduces tumor burden distal to the treatment site.  
     
     
         66 . A method according to  claim 50 , wherein said immune response comprises an immune response selected from one of the following responses: an inflammatory response, a humoral response, a cellular response, a Th1 type response, or a Th2 type response.  
     
     
         67 . A method according to  claim 66 , wherein said immune response reduces tumor burden distal to the treatment site.  
     
     
         68 . A method according to  claim 50 , wherein said immune response prolongs the survival of a tumor-bearing mammal.  
     
     
         69 . A method according to  claim 66 , wherein said immune response prolongs the survival of a tumor-bearing mammal.