Methods of treating cancer using bacteria expressing c-di-AMP
Described herein are methods of treating or preventing cancer in a subject comprising administering to the subject an effective amount of a bacteria comprising and expression vector encoding a di-adenylate cyclase enzyme.
1. A method of inducing IFN-β expression in a subject by administering to the subject an effective amount of a strain of Mycobacterium selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis bacillus , Calmette Guerin BCG, wherein said Mycobacterium comprising an expression vector encoding a di-adenylate cyclase enzyme and a pharmaceutically acceptable carrier.
2. The method of claim 1 wherein the strain of Mycobacterium is BCG.
3. The method of claim 1 wherein the expression vector is a mycobacterial expression vector.
4. The method of claim 1 wherein the expression vector comprises the DNA sequence of diadenylate cyclase (disA).
5. The method of claim 4 , wherein the disA is that of M. tuberculosis (Rv3586).
6. The method of claim 1 wherein the expression vector comprises a hsp60 promoter.
7. The method of claim 6 wherein the expression of di-adenylate cyclase enzyme or functional part thereof is regulated by a hsp60 promoter.
8. A method of inducing IFN-β expression in a subject comprising administering to the subject an effective amount of a strain of Mycobacterium selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis bacillus , Calmette Guerin BCG, wherein said Mycobacterium over-expressing diadenylate cyclase (disA), and at least one or more other compounds enhancing immunogenicity, and a pharmaceutically acceptable carrier.
9. The method of claim 8 wherein the strain of Mycobacterium is BCG.
10. The method of claim 8 wherein the at least one or more other compounds enhancing immunogenicity is c-di-AMP.
11. The method of claim 8 wherein the at least one or more compounds enhancing immunogenicity is selected from the group consisting of mycobacterial DNA, IFN, or combinations thereof.
12. The method of claim 8 wherein the expression vector is a mycobacterial expression vector.
13. The method of claim 8 wherein the expression vector comprises the DNA sequence of diadenylate cyclase (disA).
14. The method of claim 13 , wherein the disA is that of M. tuberculosis (Rv3586).
15. The method of claim 8 wherein the expression vector comprises a hsp60 promoter.
16. The method of claim 15 wherein the expression of a di-adenylate cyclase enzyme is regulated by the hsp60 promoter.
17. The method of claim 8 wherein the subject being treated has nonmuscle invasive bladder cancer.
18. The method of claim 8 wherein the subject being treated has tuberculosis.