A clinical trial has for the first time proven that an antibody called J591 specifically targets an antigen found in high amounts on both prostate tumors and on blood vessels of all solid tumors, according to a study by medical researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City.
Since the prostate-specific membrane antigen (PSMA) exists only on tumors and not other tissues, J591 armed with a drug or radiation offers a way to selectively target cancer while leaving healthy tissues unharmed, thereby resulting in very low levels of toxicity and fewer side effects for patients.
While the study, published in the Feb. 10 issue of the Journal of Clinical Oncology, was designed to prove that J591 could exclusively target tumors (it did not try to reduce tumor size), researchers now have a vehicle for selectively transporting drugs or a radioactive isotope to destroy the blood vessels that feed tumors, thereby cutting off the cancer's blood supply.
"This was a proof-of-principle study designed purely to confirm that we could successfully target tumor vasculature without targeting normal tissue," said the study's senior author, Dr. Neil H. Bander, a urological cancer specialist at the medical center and the Bernard and Josephine Chaus Professor of Urological Oncology at Weill Cornell Medical College. "Now that we have confirmed specific and accurate targeting, in subsequent studies we will arm the J591 antibody with drugs or radioactivity, and then we will assess tumor response. We are already using such armed antibodies in patients with prostate cancer and have been able to show significant anti-tumor activity."
The research team used a radioactive tracer, attached to the antibody, to follow J591's progress throughout the body. The trial involved 27 cancer patients with a wide range of solid tumors -- including kidney, bladder, lung, breast, colorectal, pancreatic and skin. All patients had widespread disease that had failed conventional treatments.
PSMA has been an attractive target for cancer drug development because it is not only present in high amounts in prostate cancers but it also is the only known molecular target that is present on tumor blood vessels but not on normal blood vessels.
Other researchers are developing drugs that indirectly starve tumors of blood by reducing the growth of new blood vessels. But, such therapies are less effective against more advanced tumors with established blood vessels. By directly targeting tumor blood vessels, however, J591 treatments could destroy the tumor's blood supply and shrink even advanced tumors.
"In the future, we envision a multipronged attack on the tumor -- for example, combining therapies aimed directly at the malignant cells, along with therapies to both directly kill the tumor's blood supply as well as prevent it from regrowing," Bander said.
This work was supported by the U.S. National Institutes of Health, U.S. Department of the Army, Cancer Research Institute, David H. Koch Foundation, Robert McCooey Cancer Research Fund, Laurent and Alberta Gerschel Foundation, Yablans Family Foundation and BZL Biologics Inc. Bander is a consultant to -- and owns stock in -- BZL Biologics, which has licensed the PSMA antibodies from Cornell.
Co-researchers, all medical doctors, include Matthew Milowsky, David Nanus, Lale Kostakoglu, Shankar Vallabhajosula and Stanley Goldsmith of NewYork-Presbyterian Hospital/Weill Cornell Medical Center and Jeffrey Ross and Christine Sheehan of Albany Medical Center.
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