Antigen Delivery Compositions And Methods Of Use

Abstract

The present invention provides antigen delivery compositions and methods of using same to prevent or to treat cancers and other infectious diseases.

1 . A method of inducing an immune response in a subject comprising administering to the subject an antigen/lipid complex comprising an antigen and a non-steroidal cationic lipid having a structure represented by the formula: 
       
         
           
           
               
               
           
         
         wherein in R 1  is a quaternary ammonium group, Y 1  is chosen from a hydrocarbon chain, an ester, a ketone, and a peptide, R 2  and R 3  are independently chosen from a saturated fatty acid, an unsaturated fatty acid, an ester-linked hydrocarbon, phosphor-diesters, and combinations thereof; 
       
       to form an antigen/lipid complex to induce an immune response to treat or prevent disease in the subject. 
     
     
         2 . The method of  claim 1  wherein said cationic lipid is selected from the group consisting of 1,2-myristoyl-3-trimethylammonium propane (DMTAP), 1,2-distearoyl-3-trimethylammonium propane (DSTAP), 1,2-palmitoyl-3-trimethylammonium propane (DPTAP), 1,2-oleoyl-3-trimethylammonium propane (DOTAP), 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine (DPEPC), 1,2-distearoyl-sn glycerol-3-ethylphosphocholine (DSEPC), 1,2-dimyristoyl-sn-glycero-3-ethylphophocholine (DMEPC), 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine (DLEPC), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), O,O′-dimyristyl-N-lysyl-aspartate (DMKE), O,O′-dimyristyl-N-lysyl-glutamate (DMKD), 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoracetate (DOSPA), N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride (DOTMA), their structural variants and derivatives, and combinations thereof. 
     
     
         3 . A method for stimulating an immune response to a tumor in a subject comprising administering to the subject the complex of  claim 1  wherein said antigen is a tumor-associated antigen thereby stimulating an immune response to a tumor in the subject. 
     
     
         4 . A method for inhibiting the growth of a tumor cell in a subject, said method comprising administering to a subject the complex of  claim 1  wherein said antigen is a tumor-associated antigen, or a tumor-associated antigen modified to retain its antigenic activity but to eliminate its tumorigenic activity, thereby preventing or inhibiting the growth of a tumor cell in said subject. 
     
     
         5 . The method of  claim 1  wherein the antigen is derived from pathogens associated with cancer risk wherein said pathogens are selected from the group consisting of hepatitis B virus, hepatitis C virus, Epstein Barr virus, HTLVL, oncogenic human papilloma viruses types 16, 18, 33, 45 and the bacterium  Helicobacter pylori.    
     
     
         6 . The method of  claim 3 , wherein the tumor associated antigen is selected from the group consisting of mutated antigens, overexpressed antigens found in tumors, melanocyte differentiation antigens, prostate associated antigens, reactivated embryonic gene products, human papilloma virus antigens, oncofetal antigens, self antigens, cancer testis antigens, mucins, gangliosides, whole cell and tumor cell lysates, immunogenic portions of whole cell and tumor cell lysates, immunoglobulin idiotypes expressed on monoclonal proliferations of B lymphocytes, and combinations thereof. 
     
     
         7 . The method of  claim 6  wherein said human papilloma virus antigen is an HPV 16 E7 protein or peptide. 
     
     
         8 . The method of  claim 7  wherein said HPV 16 E7 protein or peptide has been modified to retain its antigenic activity but to eliminate its tumorigenic activity. 
     
     
         9 . The method of  claim 1 , wherein said antigen/lipid complex includes at least one additional component selected from the group consisting of a cationic salt, an adjuvant, an immunostimulant, a cholesterol, a surfactant, a polymer, and combinations thereof. 
     
     
         10 . A method of inducing an immune response to treat or prevent an infectious disease in a subject comprising administering to the subject an antigen/lipid complex comprising an antigen and a non-steroidal cationic lipid having a structure represented by the formula: 
       
         
           
           
               
               
           
         
         wherein in R 1  is a quaternary ammonium group, Y 1  is chosen from a hydrocarbon chain, an ester, a ketone, and a peptide, R 2  and R 3  are independently chosen from a saturated fatty acid, an unsaturated fatty acid, an ester-linked hydrocarbon, phosphor-diesters, and combinations thereof; 
       
       to form an antigen/lipid complex to induce an immune response to treat or prevent an infectious disease in the subject. 
     
     
         11 . The method of  claim 10  wherein the cationic lipid selected from the group consisting of 1,2-myristoyl-3-trimethylammonium propane (DMTAP), 1,2-distearoyl-3-trimethylammonium propane (DSTAP), 1,2-palmitoyl-3-trimethylammonium propane (DPTAP), 1,2-oleoyl-3-trimethylammonium propane (DOTAP), 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine (DPEPC), 1,2-distearoyl-sn glycerol-3-ethylphosphocholine (DSEPC), 1,2-dimyristoyl-sn-glycero-3-ethylphophocholine (DMEPC), 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine (DLEPC), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), O,O′-dimyristyl-N-lysyl-aspartate (DMKE), O,O′-dimyristyl-N-lysyl-glutamate (DMKD), 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoracetate (DOSPA), N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride (DOTMA), and combinations thereof. 
     
     
         12 . The method of  claim 10  wherein said antigen is a viral or microbial antigen. 
     
     
         13 . The method of  claim 12  wherein said viral antigen is selected from the group consisting of retroviridae, picornaviridae, orthomyxoviridae, herpesviridae, hepatitis A, hepatitis B, hepatitis C, Epstein Barr virus, HTLVL, oncogenic human papilloma viruses types 16, 18, 33, and 45, and combinations thereof. 
     
     
         14 . The method of  claim 12  wherein said microbial antigen is selected from the group consisting of  Mycobacteria  species,  Pasteurella  species,  Staphylocci  species,  Streptococcus  species,  Pseudomonas  species,  Salmonella species, Helicobacter pylori , and combinations thereof. 
     
     
         15 . The method of  claim 10  wherein said antigen is a protein or peptide associated with a virus or microbe. 
     
     
         16 . The method of  claim 10  wherein said antigen is a protein or peptide associated with a virus or microbe, and the protein or peptide is modified to retain its antigenic activity but to eliminate its pathogenic activity. 
     
     
         17 . The method of  claim 10 , wherein the cationic lipid includes structural variants and derivatives thereof. 
     
     
         18 . An antigen/lipid complex comprising an antigen and a non-steroidal cationic lipid having a structure represented by the formula: 
       
         
           
           
               
               
           
         
         wherein in R 1  is a quaternary ammonium group, Y 1  is chosen from a hydrocarbon chain, an ester, a ketone, and a peptide, R 2  and R 3  are independently chosen from a saturated fatty acid, an unsaturated fatty acid, an ester-linked hydrocarbon, phosphor-diesters, and combinations thereof; 
       
       to form an antigen/lipid complex. 
     
     
         19 . The complex of  claim 18  wherein the cationic lipid is selected from the group consisting of 1,2-myristoyl-3-trimethylammonium propane (DMTAP), 1,2-distearoyl-3-trimethylammonium propane (DSTAP), 1,2-palmitoyl-3-trimethylammonium propane (DPTAP), 1,2-oleoyl-3-trimethylammonium propane (DOTAP), 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine (DPEPC), 1,2-distearoyl-sn glycerol-3-ethylphosphocholine (DSEPC), 1,2-dimyristoyl-sn-glycero-3-ethylphophocholine (DMEPC), 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine (DLEPC), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), O,O′-dimyristyl-N-lysyl-aspartate (DMKE), O,O′-dimyristyl-N-lysyl-glutamate (DMKD), 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoracetate (DOSPA), N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride (DOTMA), and combinations thereof. 
     
     
         20 . The complex of  claim 18  further including an additive selected from the group consisting of cationic salt, adjuvant, immunostimulant, cholesterol, surfactant, polymer, and combinations thereof, to improve the stability or activity of the combination. 
     
     
         21 . The complex of  claim 18  wherein the cationic lipid includes structural variants and derivatives thereof.