A newly published preclinical investigation has established that castration-resistant prostate cancer may respond well to a combination treatment encompassing immune checkpoint blockade and therapies targeting myeloid-derived suppressor cells (MDSCs).
The investigation, carried out by researchers at The University of Texas MD Anderson Cancer Center (TX, USA) and published recently in Nature, initially investigated a combination of anti-CTLA4 and anti-PD1 checkpoint inhibitors in a novel chimeric mouse model.
Observing what the team termed as “modest efficacy” with this combination, they then tested MDSC-inhibiting drugs, such as cabozantinib, in this model. MDSCs possess strong immunosuppressive abilities and are known to play a role in tumor formation and metastasis; however, targeting these cells alone was also noted to have minimal antitumor capabilities.
Following the tests of both these immunotherapies as standalone treatments, the team went on to try them in combination in their novel pancreatic model. As author Ronald DePinho (MD Anderson Cancer Center) explained: “Strikingly, both primary and metastatic castration-resistant prostate cancer responded to a combined checkpoint blockade and MDSC targeted therapeutic approach. 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 stressed how this combination would require testing in a clinical trial setting to confirm and further explore these initial results.