Anti-tumor therapy

Patent metadata

Field	Value
Publication number	US-10421971-B2
Application number	US-201415109945-A
Country	US
Kind code	B2
Filing date	Oct 24, 2014
Priority date	Jan 15, 2014
Publication date	Sep 24, 2019
Grant date	Sep 24, 2019

Abstract

Compositions, kits and methods for treating cancer in a subject in need thereof are disclosed involving one or more genes the suppression of which renders the cancer chemosensitive and/or radiosensitive.

First claim

We claim:

1. A method of treating cancer in a subject in need thereof, comprising:
regulating endogenous Type I Interferon production in the subject by maintaining a therapeutically effective amount of activation of Type I Interferon and/or inducing Type I interferon production in the subject by administering to the subject a therapeutic amount of an agent to enhance STING signaling in the subject; and
administering to the subject a therapeutic amount of ionizing radiation,
wherein the agent comprises one or more of cGAS mRNA, combretastatin A-1, combretastatin B1, CAS 181816-48, and cGAMP.

2. The method of claim 1 , further comprising suppressing the product or the expression of an Interferon-Stimulated Gene (ISG).

3. The method of claim 2 , wherein the ISG comprises at least one RIG1-like receptor (RLR) family member.

4. The method of claim 3 , wherein ionizing radiation induced Type I Interferon production is substantially maintained in the subject at levels substantially found prior to the administration of the therapeutic amount of ionizing radiation.

5. The method of claim 4 , wherein Mitochondrial Antiviral Signaling Protein (MAVS)-dependent induction of endogenous Type I Interferon production is maintained in the subject at substantially the same level found in the subject prior to the administration of the ionizing radiation.

6. The method of claim 3 , wherein the RIG1-like receptor (RLR) family member comprises LGP2 (Laboratory of Genetics and Physiology 2).

7. The method of claim 2 , wherein the suppression of the product or the expression of the ISG results in at least one of suppression of growth or proliferation of the cancer, cell death of the cancer, or sensitization of the cancer to the ionizing radiation and/or chemotherapy.

8. The method of claim 2 , wherein the suppression of the product of the ISG comprises suppression of expression of at least one Cytoplasmic Pattern-recognition Receptor (PRR) protein.

9. The method of claim 8 , wherein the at least one PRR protein comprises at least one of LGP2 and MDA5.

10. The method of claim 1 , wherein the method maintains ionizing radiation and chemotherapy sensitization in the subject.

11. The method of claim 1 further comprising down-regulating cytoplasmic DNA-sensing pathway-exonuclease TREX1 (Three Prime Repair Exonuclease 1).

12. The method of claim 1 further comprising up-regulating at least one of DAI (DNA-dependent Activator of IFN regulatory factors), IFI16 (Gamma-interferon-inducible protein Ifi-16), and Aim2 (Interferon-inducible protein AIM2).

13. The method of claim 1 , wherein the ionizing radiation comprises at least one of brachytherapy, external beam radiation therapy, or radiation from cesium, iridium, iodine, or cobalt.

14. The method of claim 1 , wherein the agent is delivered by a pharmaceutical carrier.

15. The method of 30, wherein the pharmaceutical carrier comprises at least one of a nanocarrier, a conjugate, a nucleic-acid-lipid particle, a vesicle, an exosome, a protein capsid, a liposome, a dendrimer, a lipoplex, a micelle, a virosome, a virus like particle, and a nucleic acid complex.

16. The method of claim 15 , wherein the agent is delivered into a cytosol of a dendritic cell.

17. The method of claim 1 , wherein the agent further comprises one or more of a DNA damaging agent and DNA from irradiated tumor cells.

18. The method of claim 1 , wherein the agent comprises cGAMP.

Assignees

• Univ Chicago

Inventors

• Deng Liufu
• Fu Yang-Xin
• Khodarev Nikolai
• Weichselbaum Ralph

Classifications

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K41/0038

  Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10) · CPC title

• C12N2320/31

  Combination therapy · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title