Gene Therapy For Mesothelioma

• US 20190314378A1
• Filed: 06/28/2019
• Published: 10/17/2019
• Est. Priority Date: 03/06/2016
• Status: Abandoned Application

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: STERMAN, Daniel, ALBELDA, Steven
• Application Number:
  US16/456,066
• Publication Number:
  US 20190314378A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/635 having a heterocyclic ring, e.g. sulfadiazine
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 35/761 Adenovirus
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector

Abstract

Gene therapy based combination therapy for malignant pleural mesothelioma (“MPM”) that is resistant to or recurrent after chemotherapy employing a viral vector containing a human interferon transgene, followed by standard first- or second-line cytotoxic chemotherapy. Overall survival rate was significantly higher than historical controls in the second-line group.

Claims

1. A method of treating a human patient diagnosed with mesothelioma resistant to, or recurrent after, an anti-folate and platin combination first-line treatment regimen, the method comprising:

treating said patient with a second-line treatment regimen comprising;

(i) an agent which induces the expression of interferon, in an amount effective to induce interferon expression in a human, and (ii) pemetrexed and (iii) celecoxib.

4. The method of claim 1, wherein the agent which induces the expression of interferon comprises antigen.

5. The method of claim 4, wherein the antigen comprises viral antigen.

6. The method of claim 5, where the viral antigen comprises antigenic virus.

7. The method of claim 6, where the antigenic virus comprises a transgene encoding human interferon.

8. The method of claim 7, where said antigenic virus comprises nadofaragene firadenovec.

9. The method of claim 8, where said nadofaragene firadenovec is provided in a dose of about 3×

10¹¹ viral particles, delivered intrapleurally.

10. The method of claim 1, said second line treatment regimen further comprising treatment selected from the group consisting of:

bevacizumab;

a programmed cell death-1 (PD-1) inhibitor;

a programmed cell death ligand-1 (PD-L1) inhibitor; and

a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor.

11. The method of claim 1, said second line treatment regimen further comprising treatment with celecoxib.

12. The method of claim 1, wherein said mesothelioma resistant to or recurrent after said first-line treatment regimen comprises epithelioid cancer.

20. The method of claim 10, wherein the second line treatment regimen further comprises;

a programmed cell death-1 (PD-1) inhibitor selected from the group consisting of;

pembrolizumab and nivolumab.

21. The method of claim 10, wherein the second line treatment regimen further comprises ipilimumab.

22. The method of claim 6, where the antigenic virus comprises adenovirus.

2. (canceled)

3. (canceled)

13-19. -19. (canceled)

23. A method of treating a human patient diagnosed with mesothelioma, the method comprising:

administering celecoxib, pemetrexed, a platin chemotherapeutic and an agent which induces the expression of interferon.

24. The method of claim 23, wherein the platin chemotherapeutic comprises cisplatin.

25. The method of claim 23, wherein the platin chemotherapeutic comprises carboplatin.

26. The method of claim 23, wherein the agent which induces the expression of interferon comprises antigen.

27. The method of claim 26, wherein the antigen comprises viral antigen.

28. The method of claim 27, where the viral antigen comprises adenovirus antigen.

29. The method of claim 23, wherein the agent which induces the expression of interferon comprises a transgene encoding human interferon.

30. The method of claim 23, wherein the agent which induces the expression of interferon comprises nadofaragene firadenovec.