New prostate cancer therapy developed by prof. avigdor scherz and yoram salomon

The number of men diagnosed with early-stage prostate cancer has dramatically increased in the last two decades as a result of widespread screening of prostate specific antigen (PSA) levels followed by biopsies and imaging. These patients currently face a dilemma: undergo surgery or radiotherapy—which come with the unwelcome risk of impotence and incontinence—or remain under “active surveillance,” which carries the risk of disease progression. With no midway option, an increasing number of   patients opt for the second alternative. 

But a new therapy invented by Weizmann Institute scientists Prof. Avigdor Scherz and Prof. Yoram Salomon means that patients don’t have to choose anymore between the two opposite poles of invasive treatment and active surveillance with no treatment. The new therapy—called Vascular Targeted Photodynamic Therapy used in concert with TOOKAD Soluble® (TS-VTP), enables targeted destruction of the prostate lobe containing the cancer tissue while preserving potency, continence, and overall quality of life.

Moreover, TS-VTP can be applied at any stage of active surveillance if the cancer progresses, rather than shifting immediately to the more morbid options. It can also be repeated, with similar rates of success, and does not preclude surgery to remove the prostate or radiotherapy if cancer progresses locally.

The therapy, which was clinically developed by Steba Biotech of Luxembourg in ongoing collaboration with the scientists, was recently approved by Cofepris, the Mexican Health Authority, for medical use in patients with early-stage prostate cancer. It is currently under consideration for approval by the European Medicines Agency (EMA), which regulates drug and device approvals in 27 European countries.

The Mexican approval comes after about 80 percent of patients evidenced a local cure in the treated prostate a year after treatment while maintaining potency and continence, and in the wake of the recent successful completion of a Phase III clinical trial of more than 400 patients in 43 medical centers across 11 European countries. The European study compared disease progression in TS-VTP treated patients and patients that underwent active surveillance.

The majority of the TS-VTP treated patients were home free in a few hours after treatment and back to normal activities a few days later—with none of the side effects usually encountered by the radically treated patients.

A viable solution

The therapy involves intravenously infusing patients for 10 minutes with TOOKAD® Soluble, which is non-toxic to both the tumor and normal tissues unless exposed to light. The infusion is immediately followed by confined tissue exposure to 22 minutes of near-infrared illumination delivered through miniscule optical fibers into the prostate tissue. The illumination triggers a cascade of events leading to the tumor’s destruction. It generates the release of short-lived oxygen and nitric oxide radicals, which rapidly destroy the blood vessels that nourish the diseased prostate tissue, leading to its destruction—all while leaving the healthy surrounding structures intact. The procedure takes about 90 minutes and the drug clears from the body rapidly (within about three to four hours).  

It’s a breakthrough that could hold promise for many of the hundreds of thousands men who are diagnosed with early-stage prostate cancer worldwide.

And there may be more good news ahead: The ongoing research on TS-VTP at the Weizmann Institute and collaborating labs at Memorial Sloan Kettering Cancer Center (MSKCC) in New York has shown that TS-VTP may work for advanced cancers as well. With the support of the Thompson Foundation, four clinical trials in various phases are poised to start this coming year in MSKCC.

Lessons from photosynthesis

The story of the development of TS-VTS has all the components of a great scientific success story: fruitful collaboration between different scientific disciplines, and in this case, the serendipitous turn of events that turned a chemist and plant scientist into an inventor of a cancer therapy; a commercial entity that invested in and collaborated on a highly innovative idea and remained committed through the ups and downs; a partnership with international hospitals and world-leading physicians; and enthusiastic donors who believed in the research and in the scientists driving it.

TS-VTP is based on research that took place over the course of two decades in the labs of Prof. Scherz of the Department of Plant Sciences and Prof. Salomon from the Department of Biological Regulation—a collaboration that sprung up from a hallway conversation between two friends.

“We weren’t thinking, ‘How do we cure prostate cancer,’” recalls Prof. Scherz. “We were curious as to whether we could find a way to combine principles of photosynthetic light conversion and our knowledge about cancer for selectively eliminating cancerous tissue, while not destroying the surrounding normal structures.”

"Upon illumination of circulating TS in the tumor, vasculature blood supply to the tumor is blocked and tumor destruction is initiated with an astounding precision," elucidates Prof. Yoram Salomon. He further explains: "The chain of events that follows was unprecedented and was carefully analyzed. The entire mechanism and the respective treatment protocol that we successfully developed represent a unique mode among anti-tumor treatments of which we are very proud." 

At the time the duo began their joint research, in the early 1990s, other types of photodynamic therapy existed, but they weren’t effective for the destruction of thick, solid tumors or else they were toxic, with patients at risk of major skin toxicities for up to 50 days. The PDT methods were also not selective enough to effectively distinguish between the tumor and healthy tissue.

That initial hallway conversation consisted, essentially, of this: Nature has supplied photosynthesis with bacteriochlorophylls, the photosynthetic pigment of certain aquatic bacteria that draw their energy supply from sunlight. They could be the ideal molecules for generating toxic radicals deep in tissue under the right illumination, the scientists surmised. Administering these molecules to cancer patients followed by local illumination should then lead to tumor necrosis—similar to the body’s way of eliminating malfunctioning organs. And of course the therapy would have to be safe and cause few or no side effects.

An early investment by Steba got them off to a start, and after attempting some 200 derivatives (molecules) of bacteriochlorophyll, the scientists finally arrived at the current drug combination. Yeda Research and Development Co. Ltd., the Weizmann Institute’s tech transfer arm, licensed rights to Steba in 1996.

Says Raphael Harari, owner of Steba Biotech, “I carefully examined this idea and strongly believed that it would succeed in offering a therapy while preserving the patient’s quality of life… Truly, I did not anticipate that it would take several hundreds of millions of dollars and two decades to be translated and approved in the clinical setting. But we believed in it and knew that it was important to develop effective means to prevent cancer progression while maintaining men’s wellbeing in family and society. The very good personal and professional relationships established between myself, Avigdor, Yoram, and the people of Yeda greatly helped as we experienced failures and successes over time.”

Amir Naiberg, CEO of Yeda adds: “The relationship with Steba, over 20 years, has been a close and fruitful one. The commitment made by the shareholders of Steba and their personal relationship and effective collaboration with Institute scientists and Yeda enabled this tremendous accomplishment.” 

Profs. Scherz and Salomon are also developing photodynamic therapy to treat three non-malignant ophthalmic diseases: age-related macular degeneration, a vascular disease of the retina; keratoconus, a malfunction of the cornea, which seriously impairs vision and may lead to blindness; and early-stage myopia. 

Prof. Avigdor Scherz is supported by the Leona M. and Harry B. Helmsley Charitable Trust; the Thompson Family Foundation; the Susan G. Komen Breast Cancer Foundation; Principal Anstalt; Sharon Zuckerman, Canada; and is the incumbent of the Robert and Yadelle Sklare Professorial Chair in Biochemistry.

Prof. Yoram Salomon is supported by Principal Anstalt. He is a Professor Emeritus at the Weizmann Institute was the incumbent of Charles and Tillie Lubin Professorial Chair for Biochemical Endocrinology until his retirement in 2009. He and Prof. Scherz collaborated on other research. Since 2009, Prof. Salomon acts as a consultant in these projects.

 

 

 

Prof. Avigdor Scherz and Prof. Yoram Salomon