Institute scientists reported on the new development at the Conference on Chemical Modifiers of Cancer Treatment in Clearwater, Florida, last week.
Photodynamic therapy or PDT, in which light activates cancer- killing drugs, has generated enormous interest in the medical world in recent years. However, currently PDT has several limitations: it is effective only against relatively flat and thin tumors, such as certain types of skin and bladder cancers, and patients undergoing PDT must avoid the sun for weeks following treatment because their skin becomes overly sensitive to strong light.
The new materials, derived from chlorophyll, the green pigment that allows plants to capture sunlight, may now overcome these problems. These "green" materials may make it possible to apply PDT to bulky solid tumors. Moreover, patients may need to avoid the sun for only a day or two after therapy.
The materials, developed by Profs. Avigdor Scherz of the Institute's Plant Sciences Department and Yoram Salomon of the Biological Regulation Department, were shown to kill cancer cells in tissue culture and in mice. The Dutch company Steba Beheer NV is now developing them for clinical use worldwide.
"If successful, in the future our 'green' PDT could be a powerful new tool in the struggle against cancer," says Prof. Scherz.
Minimizing side effects
PDT uses drugs that become toxic only when exposed to light. First, the drug is injected into the bloodstream or the tumor. Then, the tumor is exposed to light in a controlled manner. As a result, the drug is activated and destroys tumor cells while having little affect on healthy tissues.
"The great advantage of this treatment over conventional chemotherapy is that the drug's action is confined to the illuminated tumor site, so that the damage to healthy tissues is minimized and side effects are significantly reduced," says Prof. Salomon.
Existing light-sensitive materials used clinically as PDT drugs are most commonly based on heme, the red pigment derived from hemoglobin. They are activated only by visible light, which has limited tissue-penetrating capacity. Moreover, they work only in the presence of oxygen, which is in short supply inside many bulky tumors. Therefore, they can destroy only thin and flat tumors or tumors in early stages of development.
In contrast, the Weizmann Institute materials - derived from the green chlorophyll pigments that make green plants and photosynthetic bacteria such effective light-collectors - can be applied to larger solid tumors. This is because these materials, in addition to visible light, also absorb the near-infrared light that penetrates much deeper into body tissues. Moreover, "green" materials can work under hypoxic conditions, where oxygen levels in tissues are below normal. These properties render them superior to existing photosensitive drugs.
Another advantage of the new chlorophyll derivatives is that they clear out of the body much faster than existing drugs. This property is due to the fact that the new materials have been modified to make them soluble in water, which in turn speeds their removal from tissues. As a result, patients can tolerate outdoor light shortly after treatment without fearing that the photosensitive materials will harm their skin. The solubility also makes the materials easier to administer to patients.
A precise delivery
To deliver their materials precisely to the desired site, the scientists can attach them to antibodies, or other molecules, that act as "guided missiles," transporting the "green" materials to the target in the body.
When illuminated, the new materials were found to first destroy the blood vessels that feed the tumor. Without these vessels, the tumor cannot develop or even survive. Then, the materials destroy the tumor itself.
Tumors that are close to the body surface can be exposed to direct illumination. When a bulky tumor lies deeper within the body, it can be illuminated with a fiberoptic light guide.
The materials have successfully eradicated relatively large malignant melanoma tumors in mice. In tissue culture, they have destroyed other cancer cell types, including breast and colon.
The effectiveness of the new materials in humans will soon be tested by Steba Beheer NV, which is planning to conduct clinical trials worldwide.
The scientists are also exploring the potential use of the new materials as antimicrobial drugs. A new study showing that the targeted chlorophyll derivatives effectively kill disease-causing bacteria was published in the December 1997 issue of Photochemistry and Photobiology, the journal of the American Society for Photobiology.
This application of the new chlorophyll derivatives may be particularly important in light of the growing problem of bacterial resistance to antibiotics.
Prof. Scherz heads the Avron-Willstaetter Minerva Center for Research in Photosynthesis at the Weizmann Institute.
Prof. Salomon holds the Charles W. and Tillie K. Lubin Chair in Hormone Research.
The development of "green" PDT for clinical use is being funded by Steba Beheer NV, which has been granted a worldwide license for the product by Yeda Research and Development Co., the Weizmann Institute's technology transfer arm. Funding for basic research is also provided by the Lynn and William Frankel Fund for the Diagnosis and Treatment of Ovarian and Breast Cancer, in Philadelphia, Pennsylvania; the Jaffe Family Foundation, in Weston, Connecticut; Mrs. Sharon Zuckerman, of Toronto, Canada; Yeda Research and Development Co. Ltd.; the Israel Ministry of Science; the European Commission, and, as of January 1998, by the German-Israeli Foundation.
The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,500 scientists, students, technicians, and engineers pursue basic research in the quest for knowledge and enhancement of the human condition. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities.