For Metastatic Prostate Cancer, a Trojan Horse with a Toxic Payload


Metastatic prostate cancer is notoriously difficult to kill. The cells don't divide as quickly as those of other cancer cells, so they can't be felled by chemotherapy drugs that target rapidly growing cancers. Second, by the time prostate cancer has spread far beyond the prostate, only part of it is responsive to hormonal therapy; the rest is unfazed when the male hormones are shut down. Third,it is very hard to know exactly where metastatic prostate cancer is hiding in the body. Some of it can be seen, if it has established itself in the bone. But a few hard-core cancer cells drifting around in the bloodstream or even in another organ, such as the liver, can remain undetected indefinitely.

Now John Isaacs, Ph.D., and colleagues have developed and validated in preclinical testing a "Trojan horse" that uses stem cells and delivers a toxic payload only to metastatic prostate cancer cells. Based on the foundation of their work, the first clinical tests of this agent are set to begin in men with advanced prostate cancer.

This approach uses a certain type of stem cells, called mesenchymal stem cells. The huge benefit of these particular cells is that they come from healthy adults who donate bone marrow, cause no immune reaction – which means that no immune-suppressing drugs need to be taken and the recipient won't reject them – and they can be cultivated in the laboratory using already-approved methods. "This is an exciting milestone in research," says Isaacs, "because no trial has ever evaluated these cells in any cancer patient, including those with prostate cancer."

This therapy, which will be given intravenously, was developed by a multidisciplinary team of scientists based at several centers, including Isaacs and Samuel Denmeade, of the Chemical Therapeutic Program of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Neil Bhowmick of the Uro-Oncology Research Program of the Samuel Oschin Comprehensive Cancer Institute at the Cedars-Sinai Medical Center; Jeffrey Karp, Co-Director of Regenerative Therapeutics at the Brigham and Woman's Hospital at Harvard; and Alan Partin and Trinity Bivalacqua at the Brady Urological Institute. The group has been awarded a twoyear Challenge Award from the Movember Foundation/Prostate Cancer Foundation to begin the clinical trial, which will be led by Denmeade, Partin, and Bivalacqua. In other preclinical tests, Bhowmick, Denmeade and Isaacs are also investigating cancer-killing microparticles, to be loaded into the stem cells, and will select the most promising microparticles for future clinical development. These studies are supported by a Department of Defense Synergistic Idea Award, for which Isaacs is the principal investigator.

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