Roswell Park Researchers Publish Findings on Agent Shown to Enhance Immunotherapy

Conclusions from study of entinostat combination to be tested in kidney, prostate cancer clinical trials

BUFFALO, NY — Preclinical research by a team from Roswell Park Cancer Institute (RPCI) has demonstrated for the first time the way in which a class I histone deacetylase (HDAC) inhibitor, entinostat, appears to boost the effectiveness of cancer immunotherapy for treatment of some solid tumors. The findings support conclusions from earlier studies and also suggest that the approach merits further testing in clinical settings.

In a study involving models of renal and prostate cancer, recently published in the peer-reviewed scientific journal PLoS One, a team led by Roberto Pili, MD, Professor of Oncology, Chief of the Genitourinary Section and Co-leader of the Genitourinary Program, Department of Medicine, demonstrated the novel immunomodulatory effect through which entinostat, manufactured by Syndax Pharmaceuticals, Inc., appears to enhance the antitumor activity of Interleukin-2 (IL-2) for kidney cancer and of a survivin cancer vaccine (SurVaxM), developed at RPCI by Michael Ciesielski, PhD, and Robert Fenstermaker, MD, of the Department of Neurosurgery, for prostate cancer.

“Entinostat has an immunomodulatory effect on regulatory T cells, which are like brakes for the immune system and are present in many tumors,” Dr. Pili explains. “By suppressing these suppressor cells, entinostat releases the brakes and helps the immunotherapies to work better.”

The combination of a vaccine with approaches to deplete or suppress regulatory T cells, the researchers write, “represents a rational strategy in prostate cancer therapy” and one that “also has promising potential to be effective in other immunotherapies and in different tumors.”

Li Shen, PhD, a postdoctoral associate in the Department of Medicine, was lead author on the study. Drs. Ciesielski and Fenstermaker were also contributing authors, as were Swathi Ramakrishnan, Kiersten M. Miles, PhD, Leigh Ellis, PhD, and Paula Sotomayor, Department of Medicine; and Protul Shrikant, PhD, Department of Immunology.

The PLoS One article is titled “Class I Histone Deacetylase Inhibitor Entinostat Suppresses Regulatory T Cells and Enhances Immunotherapies in Renal and Prostate Cancer Models,” and can be accessed online at:http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030815.

A clinical study testing the combination of entinostat with IL-2 in renal-cell cancer is underway at RPCI and other sites. For more information about that study, which is currently accruing participants, go to: http://www.roswellpark.org/clinical-trials/list/145208-0.

Additional clinical studies of the combination of entinostat and other immunotherapies are planned in prostate cancer and other solid tumors.