Combining immune checkpoint inhibitors with drugs that target a population of myeloid-derived suppressor cells (MDSCs) may offer hope for men with metastatic prostate cancer who no longer respond to androgen deprivation therapy (ADT).
“A significant number of advanced prostate cancer patients treated with a chemical castration therapy called androgen deprivation therapy experience relapse with relentless progression to lethal metastatic, castration-resistant prostate cancer,” cancer biology professor Ronald DePinho, MD, said in a news release. “While immune checkpoint blockade therapy is effective in many cancers, it has been less successful for this particular form of prostate cancer, which has motivated a search for targeted therapies that overcome this resistance.”
In an attempt to find novel treatment options for men with metastatic castration-resistant prostate cancer, researchers first tested a combination of anti-CTLA-4 and anti-PD-1 immune checkpoint blockers in prostate cancer mouse models. But according to study first author Xin Lu, PhD, the combination showed only modest efficacy.
The researchers knew that tumors often contain immunosuppressive cells that are associated with poor prognosis and response to immunotherapies. They hypothesized that blocking the immunosuppressive cells known as MDSCs could help these men.
While MDSC-blocking drugs such as cabozantinib and BEZ also had minimal anti-tumor effects, the team found that combining these agents with immune checkpoint inhibitors slowed tumor growth in mice.
“Strikingly, both primary and metastatic castration-resistant prostate cancer responded to a combined checkpoint blockade and MDSC targeted therapeutic approach,” said DePinho. “These observations in mouse models of prostate cancer, using a sophisticated genetic approach developed by James Horner at MD Anderson, illuminate a clinical path hypothesis for combining immune checkpoint blockades with MDSC-targeted therapies in the treatment of this aggressive cancer.”
DePinho said clinical trials must now test this combination in prostate cancer patients, and urged researchers to explore this combination with standard-of-care treatment for both newly diagnosed prostate cancer patients as well as for men with established castration-resistant prostate cancer.