Genetically modified tumor-targeted bacteria with reduced virulence
View Patent ↗The present invention is directed to mutant Salmonella sp. having a genetically modified msbB gene in which the mutant Salmonella is capable of targeting solid tumors. The invention is also directed to Salmonella sp. containing a genetically modified msbB gene as well as an genetic modification in a biosynthetic pathway gene such as the purl gene. The present invention further relates to the therapeutic use of the mutant Salmonella for growth inhibition and/or reduction in volume of solid tumors.
1. A method of inhibiting the growth or reducing the volume of a solid tumor cancer, comprising administering an effective amount of a mutant Salmonella sp. to a patient having a solid tumor cancer, wherein said mutant Salmonella sp. comprises a disrupted msbB gene and is capable of targeting a solid tumor cancer when administered in vivo.
2. The method of claim 1 , wherein the mutant Salmonella sp. is Salmonella typhi, Salmonella choleraesuis , or Salmonella enteritidis.
3. The method of claim 1 , wherein the mutant Salmonella sp. expresses an altered lipid A molecule.
4. The method of claim 1 , wherein the mutant Salmonella sp. induces TNFα expression at about 5 percent to about 40 percent of that induced by a wild-type Salmonella sp.
5. The method of claim 1 , wherein the mutant Salmonella sp. induces TNFα expression at about 10 percent to about 35 percent of that induced by a wild-type Salmonella sp.
6. The method of claim 1 , wherein a chelating agent inhibits the growth of the mutant Salmonella sp. by about 90 percent compared to the growth of a wild-type Salmonella sp.
7. The method of claim 1 , wherein a chelating agent inhibits the growth of the mutant Salmonella sp. by about 99 percent compared to the growth of a wild-type Salmonella sp.
8. The method of claim 1 , wherein a chelating agent inhibits the growth of the mutant Salmonella sp. by greater than 99 percent compared to the growth of a wild-type Salmonella sp.
9. The method of claim 6 , wherein the chelating agent is Ethylenediaminetetraacetic Acid (EDTA), Ethylene Glycol-bis(β-aminoethyl Ether) N,N,N′,N′,-Tetraacetic Acid (EGTA), or sodium citrate.
10. The method of claim 1 , wherein the mutant Salmonella sp. survives in macrophages at about 50 percent to about 30 percent of the level of survival of a wild-type Salmonella sp.
11. The method of claim 1 , wherein the mutant Salmonella sp. survives in macrophages at about 30 percent to about 10 percent of the level of survival of a wild-type Salmonella sp.
12. The method of claim 1 , wherein the mutant Salmonella sp. survives in macrophages at about 10 percent to about 1 percent of the level of survival of a wild-type Salmonella sp.
13. The method of claim 1 , wherein the solid tumor cancer is melanoma, colon carcinoma, lung cancer, liver cancer, kidney cancer, prostate cancer, or breast cancer.