Immuno-Gene Combination Therapy
“In situ vaccination” using immuno-gene therapy has the ability to induce polyclonal anti-tumor responses directed by the patient's immune system. Patients with unresectable MPM received two intrapleural doses of a replication-defective adenoviral vector containing the human interferon-alpha (hIFN-α2b) gene (Ad.IFN) concomitant with a 14-day course of a cyclooxygenase-2 inhibitor (celecoxib), followed by standard first- or second-line cytotoxic chemotherapy. Forty subjects, ECOG PS 0 or 1, were treated: 18 received first-line pemetrexed-based chemotherapy with platinum, 22 received second-line chemotherapy with pemetrexed (n=7) or a gemcitabine-based regimen (n=15). 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; 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
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 1 , wherein said cancer resistant to or recurrent after said first-line treatment regimen is selected from the group consisting of: malignant pleural mesothelioma, non-small cell cancer and bladder cancer.