Immunomodulatory minicells and methods of use
The present disclosure is related to immunomodulatory bacterial minicells and methods of using the minicells.
1. A bacterial minicell, comprising perfringolysin O, wherein the minicell is capable of exerting an immunomodulatory anti-tumor effect following administration to a subject.
2. A bacterial minicell according to claim 1 that further comprises one or more biologically active compounds.
3. A bacterial minicell according to claim 2 wherein the one or more biologically active compounds are selected from the group consisting of small molecules, nucleic acids, polypeptides, radioisotope, lipids, lipopolysaccharides, and any combination thereof.
4. A bacterial minicell according to claim 1 that further comprises invasin.
5. A bacterial minicell according to claim 4 wherein the invasin is a Yersinia pseudotuberculosis invasin.
6. A bacterial minicell according to claim 1 that further comprises a protein toxin.
7. A bacterial minicell according to claim 6 wherein the protein toxin is selected from the group consisting of a catalytic fragment of diphtheria toxin, gelonin, Pseudomonas exotoxin A, and ricin A.
8. A bacterial minicell according to claim 1 that further comprises an exogenous polypeptide that is not a protein toxin.
9. A bacterial minicell according to claim 1 that is a Th1 immunomodulatory minicell.
10. A bacterial minicell according to claim 2 that is a Th1 immunomodulatory minicell.
11. A bacterial minicell according to claim 1 that further comprises one or more Th1 cytokines, one or more pore forming cytolysin proteins, one or more phospholipases, or one or more immunomodulatory nucleic acids.
12. A bacterial minicell according to claim 11 wherein the Th1 cytokine is selected from the group consisting of IL-2, GMCSF, IL-12p40, IL-12p70, IL-18, TNF-α, or IFN-γ.
13. A composition comprising a bacterial minicell according to claim 1 and a physiologically acceptable carrier.
14. A composition according to claim 13 that comprises minicell-producing viable parental cell contamination of less than 1 in 10 5 minicells.
15. A composition according to claim 13 formulated as a dry or liquid composition.
16. A pharmaceutical composition comprising a bacterial minicell according to claim 1 and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition according to claim 16 that comprises minicell-producing viable parental cell contamination of less than 1 in 10 10 minicells.
18. A pharmaceutical composition according to claim 16 formulated as a dry or liquid composition.
19. A pharmaceutical composition according to claim 16 formulated as a liquid composition for parenteral administration.