Improving immune responses in prostate cancer

Men with high-risk prostate cancer who received immunotherapy treatment with enoblituzumab in the weeks leading up to surgery had favorable rates of disease remission and tumor downgrading after surgery, according to a recent study published in Nature Medicine.

Clinical trials are planned to further evaluate the findings.

Prostate cancer is the second most common type of cancer in men. Roughly 13 out of every 100 American men will be diagnosed with prostate cancer during their lifetime, according to the Centers for Disease Control and Prevention.

The current standard treatment for localized prostate cancer is radiation or surgical removal of all or part of the prostate. In the case of high-risk patients, the cancer will return or metastasize after treatment nearly 70 percent of the time. For men who present with advanced disease, there are currently no curative options.

In other cancers, like renal cell carcinoma, lung cancer and cancers of the colon and rectum, immune-mediated therapies have demonstrated high efficacy. Prostate cancer, however, does not appear to be as naturally immune-responsive.

In the current study, in an attempt to activate prostate cancer-killing immune cells, investigators at Johns Hopkins Hospital administered enoblituzumab to 32 men with high-risk prostate cancer prior to prostatectomy. Enoblituzumab, a monoclonal antibody, works by targeting B7-H3, a protein associated with prostate cancer and is related to a family of immune checkpoint molecules. Of the 32 men enrolled in the study, half of men had their cancer appear less aggressive at surgery and 21 had undetectable levels of prostate cancer-specific antigen one year after treatment. Further, there were signs of immune activation within the prostate.

The findings point to enoblituzumab as a safe treatment option for prostate cancer that needs further study, said Ashley Ross, MD, PhD, associate professor of Urology and co-author of the study.

“Prostate cancer is typically thought of as an immune inactive tumor; It’s not very immune responsive,” said Ross, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “What we wanted to determine was if we administered this molecule to patients with prostate cancer, would the antibody get into the prostate, bind with its target and direct the immune system to cancerous cells.”

“What we found was that enoblituzumab was very well tolerated, and did in fact reach its target,” Ross said. “All men on the study received enoblituzumab. Regardless, in comparison to similar patients who did not receive the drug and had surgery, short-term cancer related outcomes appeared improved.”

Clinical trials are planned to further evaluate the findings, according to the study.

This study was supported by MacroGenics, Inc.