Inspiring Research in Immunotherapy
“Immunotherapy represents a new frontier in genitourinary cancers,” says Charles G. Drake, MD, PhD, Director, Genitourinary Oncology and Co-Director of Cancer Immunotherapy, NewYork-Presbyterian/Columbia University Irving Medical Center. “We are looking at how these therapies can be used synergistically with traditional therapies in prostate, kidney, and other urological cancers to improve outcomes.” Under Dr. Drake’s leadership, the GU oncology group at Columbia has nearly 30 ongoing clinical trials.
When Dr. Drake’s research team discovered that standard hormonal therapy, despite initially appearing to activate the immune system to attack prostate cancer, is in fact leaving prostate cancer cells behind, they turned their attention to a chemical called interleukin-8 (IL-8). “The cancer cells that do not respond to hormonal therapy secrete IL-8, which attracts a population of cells that turns off an immune response to the tumor,” explains Dr. Drake. “There are a number of ways to target these cells. Our idea was to stop them from ever getting in there in the first place. IL-8 leaves a ‘trail of bread crumbs’ that these harmful, suppressive immune cells use to find their way into the tumor. By blocking IL-8, we could conceal this trail, preventing the suppressive cells from entering the tumor.”
Dr. Drake and his colleague Matthew Dallos, MD, have turned this hypothesis into an innovative 60-patient trial in which androgen deprivation therapy (ADT) is combined with a novel drug aimed at preventing suppressive myeloid cells from entering the prostate tumor microenvironment at the time of therapy. “To me, this is the most exciting immunotherapy trial in all of GU cancer,” says Dr. Drake. “These are patients who have high risk prostate cancer that recurred after surgery or radiation. The MAGIC-8 study will test whether nivolumab, an anti-PD-1 antibody, with or without anti-IL-8 therapy, combined with a short course of hormonal therapy, promotes anti-tumor immune responses that prolong time to disease relapse in men with early prostate cancer.”
“In prostate cancer we might be getting a second chance at cure,” says Dr. Drake. “If the surgery or the radiation isn’t successful, attacking the tumor with this combination therapy when the cancer first recurs might lead to long-term remission.” MAGIC-8 is currently accruing patients at Columbia, Weill Cornell Medicine, and Thomas Jefferson University.
“ We are looking at how immunotherapies can be used synergistically with traditional therapies in GU cancers to improve outcomes.”
— Dr. Charles G. Drake
A first-of-its-kind pilot study has recently begun at Columbia for patients who present with stage III kidney cancer. “These patients are typically candidates for radical nephrectomy, but surgery will cure only about half of those patients,” says Dr. Drake. “This trial will evaluate the benefit of providing PD-1 targeted therapy in combination with a novel therapy directed against interleukin-1 (IL-1) before surgery to target myeloid-derived suppressor cells with the prospect of increasing the chance for cure.”
The study is, in part, informed by the research of David Aggen, MD, PhD, a former hematology/oncology fellow at Columbia, who showed that interleukin 1 is the “bad actor” in kidney cancer, supporting the growth and health of cells that are suppressive and turn off the tumor immune response. “What is particularly interesting about this trial is that not only are we trying to help the patients do better, but we are also trying to see if these two experimental drugs – canakinumab and spartalizumab – can modulate the tumor’s environment that promotes an anti-tumor immune attack,” says Dr. Drake.