Gene Therapy For Mesothelioma
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.
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.
2 . (canceled)
3 . (canceled)
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 3×10 11 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.
13 - 19 . (canceled)
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.
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.