An experimental drug developed and tested at Weill Cornell Medical College may bring new hope to men with one of the most aggressive and hard-to-treat forms of prostate cancer.
The single-dose compound, Lutetium-177-Labeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591, known for short as 177Lu-J591, has prolonged the lives of men with metastatic castration-resistant prostate cancer — historically an aggressive, resistant and lethal cancer for which there are now new treatment options.
177Lu-J591 combines a radioactive agent bound to an antibody. The antibody, J591, targets prostate-specific membrane antigen, a protein produced by the prostate that is overexpressed in cancers of that gland, and releases radiation into each individual tumor cell. The action of the compound is to locate, radiate and shrink the cancer. Prostate-specific antigen levels and scans monitor the response to treatment, with the goal to prolong patients' lives. A Phase 2 clinical trial at Weill Cornell published last month in Clinical Cancer Research, showed that the majority of patients who took the drug lived longer than traditional treatment predicts they would.
"Our results are exciting," said Dr. Scott T. Tagawa, associate professor of clinical medicine and associate professor of clinical urology at Weill Cornell, who performed the trial. "We have really gone from the bench to the bedside with the development of this therapy, which we've done internally. It's particularly exciting to watch 177Lu-J591 progress from the lab bench, to mice, to men and have a positive impact."
J591 has its roots in the lab of Dr. Neil H. Bander, director of urological oncology research, the Bernard and Josephine Chaus Professor of Urological Oncology and professor of urology at Weill Cornell. A urologic oncologist, Dr. Bander set out more than two decades ago to develop monoclonal antibodies, laboratory-produced molecules that mimic antibodies that the immune system naturally generates against germs, vaccines and other invaders. Researchers engineer monoclonal antibodies to attach to specific molecular markers in cancer cells.
After successfully developing the world's largest panel of monoclonal antibodies to kidney cancer in the early '90s, Dr. Bander turned his attention to prostate cancer and generated the first series of antibodies to prostate-specific membrane antigen that could bind to viable prostate cancer cells. The monoclonal antibody J591 is a recent product of this research.
Dr. Neil Bander
After additional research showed that the antibody can precisely locate prostate cancer cells in patients, Dr. Bander began investigating therapeutic agents that could be targeted by J591 and deliver the tumors' fatal blow. Enter radioisotope Lutetium-177.
"Over the last 10 years, monoclonal antibody-based drugs have transformed the treatment of many diseases, including the treatment of several types of cancers," Dr. Bander said. "My lab team succeeded in developing the first such antibodies capable of effectively targeting prostate cancer cells wherever they are in the body while avoiding normal cells. This core technology is allowing us to develop a variety of diagnostic and therapeutic agents of which 177Lu-J591 is the first."
Dr. Bander, Dr. Tagawa and their teams are now translating their discoveries into new prostate cancer therapies that are showing promise in clinical trials. 177Lu-J591 has been licensed by a pharmaceutical company which will conduct an international Phase 3 clinical trial starting in 2014 with the goal of making this therapy available to many more men with this deadly disease.
"It is gratifying to see the early data confirm very precise tumor targeting in patients that, in turn, has resulted in anti-tumor efficacy and improved patient survival," Dr. Bander said. "We have been fortunate at Weill Cornell Medical College to have a group of skilled collaborators in urologic oncology, medical oncology and nuclear medicine in order to translate our efforts from the bench to the bedside. This collaborative effort is now expanding further with the addition of several industry collaborators, each building on our technology to develop targeted diagnostic and therapeutic agents that we anticipate will provide significant benefit to cancer patients in the coming years."
177Lu-J591 helped give a 76-year-old New York City man his life back. First diagnosed with prostate cancer in the 1990s, the man, who works in the investment banking industry, had most of his prostate removed — and the disease along with it. For seven years his PSA levels remained low and steady — a sign that his cancer was in remission — until around 2000, when they began to rise. By 2007 his cancer was rampant. Diagnosed with metastatic castration-resistant prostate cancer, the banker was referred to Dr. Tagawa, a urologic oncologist.
He received hormonal therapy followed by chemotherapy, and while his PSA levels decreased, the change wasn't substantial. After doctors exhausted all the traditional lines of therapy, the banker received a single dose of the experimental drug 177Lu-J591 in 2009. His PSA levels plummeted, keeping his cancer at bay until the U.S. Food and Drug Administration could approve two new drugs that had been moving through the drug-development pipeline. He's still taking one of those medications and today, his prostate cancer is nearly undetectable. If not for the incredible work of Dr. Tagawa and his entire staff, he said, his life might have been completely different.
"It gives me so much additional confidence," the banker said of 177Lu-J591. "It gives me the desire to help people, to do things. Most people retire at this age, they do something else, volunteer. But that's not for me. I'm glad I get to keep doing what I love to do."