Cancer therapy via a combination of epigenetic modulation and immune modulation
Cancer therapies that combine epigenetic modulating agent(s) with immune modulating agent(s), which were remarkably identified to provide an improved treatment regimen over single agent therapy, are disclosed. In particular embodiments, the invention provides for improved treatment of NSCLC in patients via administration of exemplary immune modulating agents anti-PD-1 antibody or anti-PD-L1 antibody, which were observed to show enhanced activity in combination with the exemplary epigenetic modulating agent 5-deoxyazacytidine. Further, expression markers of responsive neoplastic cells are also disclosed.
1. A method of treating a neoplastic condition in a human subject in need thereof consisting of:
administering to the human subject (i) a first agent that is a DNA methyl transferase (DNMT) inhibitor and (ii) a second agent that is human or humanized anti-PD-1 antibody, thereby treating the neoplastic condition in the human subject,
wherein the neoplastic condition is lung cancer, colon cancer or ovarian cancer,
wherein the first agent is administered before the second agent, and
wherein the first agent increases PD-L1 protein level expression in the lung cancer, colon cancer or ovarian cancer.
2. The method of claim 1 , wherein said first agent is selected from the group consisting of 5-azacytidine, 5-aza-2′-deoxycytidine, and a dinucleotide containing 5-aza-CdR.
3. The method of claim 2 , wherein said first agent is 5-aza-2′-deoxycytidine.
4. The method of claim 1 , wherein said neoplastic condition is lung cancer.
5. The method of claim 4 , wherein said lung cancer is non-small cell lung cancer (NSCLC).
6. The method of claim 1 , wherein shrinkage of the neoplastic condition in said human subject occurs.
7. The method of claim 1 , wherein said administering stabilizes the neoplastic condition in said human subject.
8. The method of claim 7 , wherein said stabilization is for a duration of one month or more.