The cancer treatment field scored a nice win to kick off 2014. Past studies have hinted that epigenome modifying drugs show great potential in the clinic, but new findings from Kunle Odunsi and team at the Roswell Park Cancer Institute in Buffalo, New York has demonstrated that a combinatorial approach using Decitabine (a DNA ‘demethylater’) and a cancer vaccine can give new hope to those battling cancer.

The group exploited the fact that NY-ESO-1 is a tumor antigen with limited expression in normal tissues but then goes on to become aberrantly expressed in ovarian cancers. The research hit a big roadblock, though, when they discovered that the antigen isn’t expressed uniformly in all cancer cells, so the crew developed a clever solution to tackle this heterogeneity. The team deployed a demethylating agent, Decitabine, to even things out amongst cancers cells and, as Odunsi shares, “force the expression of NY-ESO-1 on [the rest of] the ovarian cancer cells in order to allow the immune system to recognize and attack them.”

The Roswell Park group noticed that the treatment evokes ‘antigen spreading’. Odunsi explains that “Although we immunized against a single target [NY-ES0-1], we analyzed and found that we were able to induce immune responses against three other antigens, against which we did not immunize.” …giving them a biological hat trick.

Odunsi concludes that “Although clinical results were not a focus of this phase I trial, we saw evidence of clinical benefit in up to 60 percent of the patients with chemotherapy-resistant tumors. The combination of a demethylating agent, chemotherapy, and cancer vaccine may have enabled this remarkable effect.”

Get all the combinatorial facts in Cancer Immunology Research, January 2014