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 comprising:
a. diagnosing in said patient cancer; and then b. treating said patient with a first-line treatment regimen comprising treatment selected from the group consisting of: an anti-folate and platin combination regimen; an anti-folate and platin and bevacizumab combination regimen; 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 and PD-1 or PD-L1 inhibitor combination regimen; and then
c. diagnosing in said patient cancer resistant to or recurrent after said first-line treatment regimen; and then
d. treating said patient with an agent which induces the expression of interferon, in an amount effective to induce interferon expression in a human; and then
e. treating said patient with a second-line treatment regimen comprising treatment selected from the group consisting of: pemetrexed, gemcitabine, cisplatin and carboplatin.
2 . The method of claim 1 , wherein the second-line treatment regimen comprises pemetrexed.
3 . The method of claim 1 , wherein the second-line treatment regimen comprises gemcitabine.
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 rAd.IFN.
9 . The method of claim 8 , where said rAd.IFN 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 cancer resistant to or recurrent after said first-line treatment regimen comprises epithelioid cancer.
13 . The method of claim 12 , wherein said epithelioid cancer comprises malignant pleural mesothelioma.
14 . A method of treating a human patient comprising:
a. diagnosing in said patient cancer; and then
b. treating said patient with a first-line cancer treatment regimen; and then
c. diagnosing in said patient said cancer, said cancer resistant to or recurrent after said first-line cancer treatment regimen; and then
d. treating said patient with an agent which induces the expression of interferon, in an amount effective to induce interferon expression in a human; and
e. treating said patient with an agent which inhibits an inhibitory human immune system checkpoint.
15 . The method of claim 14 , wherein said cancer comprises cancer selected from the group consisting of: bladder cancer, non-small cell lung carcinoma and mesothelioma.
16 . The method of claim 15 , wherein said cancer comprises bladder cancer.
17 . The method of claim 14 , further comprising:
f. treating said patient with a cytotoxic selected from the group consisting of: pemetrexed, gemcitabine and platinum-based cytotoxic.
18 . The method of claim 17 , wherein the cytotoxic comprises pemetrexed.
19 . The method of claim 17 , wherein the cytotoxic comprises platinum-based cytotoxic.
20 . The method of claim 14 , wherein the agent which inhibits an inhibitory human immune system checkpoint is selected from the group consisting of: pembrolizumab, nivolumab and ipilimumab.
21 . A method of treating a human patient comprising:
a. diagnosing in said patient cancer; and then
b. treating said patient with an agent which induces the expression of interferon, in an amount effective to induce interferon expression in a human; and
c. treating said patient with an agent which inhibits an inhibitory human immune system checkpoint.
22 . The method of claim 21 , the agent which inhibits an inhibitory human immune system checkpoint selected from the group consisting of: pembrolizumab, nivolumab and ipilimumab.