Compositions and methods for treatment of cancer using bacteria

Abstract

Provided herein are compositions comprising substantially non-viable Gram-negative bacterial organisms that have a substantial reduction in endotoxin activity and/or pyrogenicity and methods for treating a cancer using the same. Also provided are methods for treating cancer provided herein, comprising administering to a mammal diagnosed with cancer, substantially non-viable Gram-negative bacteria having a substantial reduction in endotoxin activity and/or pyrogenicity, in an amount sufficient to inhibit growth or metastasis of the cancer. An additional method is provided comprising administering viable or non-viable Gram-negative bacterial organisms that have a genetic defect that results in a substantial loss of lipopolysaccharide within the outer membrane of the bacteria. Further provided are methods for reducing endotoxin activity and/or pyrogenicity in Gram-negative bacteria comprising treatment with polymyxin and glutaraldehyde.

1 . A composition comprising substantially non-viable Gram-negative bacterial organisms having a substantial reduction in endotoxin activity and/or pyrogenicity and a pharmaceutically acceptable excipient. 
     
     
         2 . (canceled) 
     
     
         3 . The composition of  claim 1 , wherein at least about 90% of the organisms are non-viable. 
     
     
         4 . The composition of  claim 1 , wherein about 100% of the organisms are non-viable. 
     
     
         5 . The composition of  claim 1 , wherein the endotoxin activity and/or pyrogenicity is reduced by about 75%. 
     
     
         6 . The composition of  claim 1 , wherein the endotoxin activity and/or pyrogenicity is reduced by about 85%. 
     
     
         7 . The composition of  claim 1 , wherein the endotoxin activity and/or pyrogenicity is reduced by about 95%. 
     
     
         8 . A method for treating a cancer comprising administering to a mammal diagnosed as having a cancer an amount of substantially non-viable Gram-negative bacterial organisms having a substantial reduction in endotoxin activity and/or pyrogenicity, wherein the amount administered is sufficient to inhibit growth or metastasis of the cancer. 
     
     
         9 . The method of  claim 8 , wherein the bacterial organisms are made substantially non-viable by treatment with radiation. 
     
     
         10 . The method of  claim 8 , wherein the bacterial organisms are made substantially non-viable by treatment with glutaraldehyde. 
     
     
         11 . The method of  claim 8 , wherein reduction in endotoxin activity and/or pyrogenicity is achieved by treating the bacterial organisms with an antibiotic that inactivates endotoxin. 
     
     
         12 . The method of  claim 11 , wherein said antibiotic is selected from the group consisting of polymyxin B and polymyxin E. 
     
     
         13 . The method of  claim 8 , wherein reduction in endotoxin activity and/or pyrogenicity is achieved by treating the bacterial organisms with glutaraldehyde. 
     
     
         14 . The method of  claim 8 , wherein reduction in endotoxin activity and/or pyrogenicity is achieved by treating the bacterial organisms with an antibiotic known to disrupt the biosynthesis of KDO2-Lipid IV A . 
     
     
         15 . The method of  claim 8 , wherein the organisms comprise a genetic defect that disrupts the biosynthesis of KDO2-Lipid IV A  sufficient to substantially reduce endotoxin activity and pyrogenicity. 
     
     
         16 . The method of  claim 8 , wherein the organisms comprise a genetic mutation that prevents O-acylation of KDO2-Lipid IV A  sufficient to substantially reduce endotoxin activity and pyrogenicity. 
     
     
         17 . The method of  claim 16 , wherein the defect is in the msbB or lpxM loci. 
     
     
         18 . The method of  claim 8 , wherein the cancer is a solid tumor. 
     
     
         19 - 27 . (canceled) 
     
     
         28 . The method of  claim 8 , wherein the organism is  Salmonella.    
     
     
         29 . The method of  claim 8 , wherein the organism is  Escherichia.    
     
     
         30 - 34 . (canceled) 
     
     
         35 . A method of killing and reducing endotoxin activity and/or pyrogenicity in a Gram-negative bacterial organism comprising treating said bacteria with polymyxin and glutaraldehyde. 
     
     
         36 - 38 . (canceled)