REHOVOT, Israel — Dutch company Steba Beheer NV holds the licensing rights to develop a novel chlorophyll for tumor destruction by photodynamic therapy (PDT).

"Chlorophyll pigments are nature's light-collectors, giving green plants and certain bacteria their photosynthetic abilities, so they are the natural choice for PDT drugs," said Avigdor Scherz, professor in the plant sciences department of the Weizmann Institute of Science, in Rehovot.

The new chlorophyll derivatives were the fruits of a collaboration between Scherz and Yoram Salomon, professor in the department of biological regulation. They were shown to induce complete eradication of relatively large solid tumors in mice when exposed to near-infrared illumination.

Steba Beheer funded development of "green" PDT for clinical use and holds the worldwide license for the product, bought from Yeda Research and Development Co., the Weizmann Institute's technology transfer arm.

Clinical Trials Expected This Year

Nisso Zadik, Israeli representative of Steba Beheer, said, "We are now developing worldwide these plant derivatives for clinical trials, which are expected to start within 10 months. The company has decided to invest in Israel in new facilities for the production of large quantities of raw material for the worldwide clinical development."

PDT uses light to activate cancer-killing drugs. Among the first products approved by the FDA for PDT was Photofrin, which was developed by QLT PhotoTherapeutics Inc., of Vancouver, British Columbia, and cleared for marketing in December 1995.

The new materials are derived from bacteriochlorophyll, the blue-green pigment in which photosynthetic bacteria capture sunlight.

"The chlorophyll derivatives make it possible to apply PDT to bulky solid tumors and without the photosensitizing side effects," said Scherz, who is head of the Avron-Willstatter Center for photosynthesis at the Weizmann Institute

First, the drug is injected into the bloodstream attached to amino acid residues or to hormones, antibodies or other molecules that may act as "guided missiles," transporting the "green" materials to the target. Alternatively, the drugs are injected directly into the tumor. Then the tumor is exposed to illumination at near-infrared light.

"The free radicals formed by the light-sensitized drug first destroy blood vessels that feed the tumor. Without these vessels, the tumor cannot develop or even survive. In addition, because of the exposure to an overflow of the light-sensitized drug into the tumor body itself, tumor cells are also destroyed," said Salomon, who holds the Charles W. and Tillie K. Lubin Chair in Hormone Research at the Weizmann Institute.

Tumors close to the body surface can be exposed to direct illumination. Deeper-lying bulky tumors can be illuminated with a fiberoptic light guide under endoscopic control, aided by imaging techniques such as magnetic resonance or ultrasound.

"The great advantage of this treatment over conventional chemotherapy is that toxicity is both enhanced and confined to the illuminated tumor site, significantly reducing damage to healthy cells and thus also systemic side effects," Salomon told BioWorld International.

Deep Penetration Into Tissues Possible

When applied to mice, relatively large malignant melanoma tumors subcutaneously implanted were eradicated entirely. In tissue culture, the green PDT destroyed other cancer cell types as well, including breast and colon.

Photofrin and other photosensitive materials currently used clinically for PDT are based on heme, the red pigment derived from hemoglobin. They are activated by visible light only, which limits the tissue-penetrating capacity of the exciting light beam.

In addition to visible light, the green pigments also absorb near-infrared light — which penetrates much deeper into body tissues — allowing them to be applied to larger solid tumors. And they can work under hypoxic conditions. Moreover, the new chlorophyll derivative drugs have been made soluble in water, making them easier to administer and able to clear tissues much faster than existing drugs.

"Patients will enjoy the immediate benefits of improved therapy with fewer toxic side effects, and the convenience of tolerating outdoor light even shortly after treatment without fear that the photosensitive materials will harm their skin," Zadik said.

The scientists also are exploring the potential use of the new chlorophyll-derived materials as antimicrobial drugs. A new study published in the December 1997 issue of Photochemistry and Photobiology, the journal of the American Society for Photobiology, shows that the targeted chlorophyll derivatives effectively kill disease-causing bacteria.

"This application of the new chlorophyll derivatives may prove a new avenue of approach to the growing problem of bacterial resistance to antibiotics," Scherz said. "We are currently investigating this avenue."

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