COMPOSITIONS AND METHODS FOR TREATMENT OF CANCER USING BACTERIA
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)