Combination immunotherapy shows promise in castration-resistant prostate cancer

Researchers at the University of Texas MD Anderson Cancer Center have found that castration-resistant prostate cancer responds well to a combination treatment comprised of immune checkpoint blockades and myeloid-derived suppressor cell (MDSC)-targeting therapies.

The researchers tested a range of checkpoint blockades in combination in mouse models, including anto-CTLA4 and anti-PD1, finding them to present "modest efficacy". MDSC-inhibiting drugs including cabozantinib and BEZ showed similarly weak effects when used in isolation. However, when both checkpoint blockades and MDSC-inhibitors were used in combination, the therapy proved much more successful.

"A significant number of advanced prostate cancer patients treated with a chemical castration therapy called androgen deprivation therapy (ADT) experience relapse with relentless progression to lethal metastatic, castration-resistant prostate cancer," explained Ronald DePinho, Professor of Cancer Biology. "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."

"Strikingly, both primary and metastatic castration-resistant prostate cancer responded to a combined checkpoint blockade and MDSC targeted therapeutic approach," he continued. "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."

The team now plans to move towards testing the therapy in clinical trials in order to validate its effectiveness in combination with anti-androgen drugs for the both the castration-resistant indication and for newly diagnosed cases.

Matt Fellows