"We're developing a new therapy for cancer treatment. We injected a mouse with a non-toxic chemotherapy drug that you make toxic by illuminating the tumor. When you turn off the light, that's it," explains Professor Yoram Salomon, Biological Regulation Department, about the research he is conducting with Professor Avigdor Scherz, Plant Sciences Department.
The drug he is referring to is a water soluble derivative of chlorophyll, which is the green pigment of plants. Chlorophyll is the light-harvesting molecule, the antenna of this planet that harvests solar energy, later transforming it into useable fuels. Scherz and Salomon are taking this molecule and utilizing it for a completely different purpose.
They are applying the chlorophyll to photodynamic therapy, or PDT, a cancer treatment already in common use. The essential element in understanding PDT is that it uses a combination of drugs and light. Simply stated, the drug is injected into the patient's or animal's bloodstream, or directly into the tumor. Then, by exposing only the tumor to light in a controlled manner, the drug is activated and becomes toxic to cancer. Result: The drug-and-light combination destroys tumor cells while having little effect on healthy tissues.
However, states Salomon, "For the drugs used today, there are limitations." That's why their work is so important. PDT as it is currently practiced in a clinical setting is effective only against relatively flat and thin tumors, such as certain types of skin and bladder cancers. The new tandem approach promises to destroy tumors, the bulky, solid tumors that until now have been impenetrable by light.
Another limitation for patients undergoing standard PDT is that they must avoid sunlight for weeks following treatment because their skin becomes overly sensitive to strong light. In contrast, the "green" materials, which are modified to make them soluble in water, clear faster from the body. That may allow patients to tolerate outdoor light within a few days after treatment with less concern that the photosensitive materials will harm their skin.
"If successful, in the future our 'green' PDT could be a powerful new tool in the struggle against cancer," says Scherz. "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," reports Salomon.
The materials were shown to kill cancer cells in tissue culture and they have successfully eradicated relatively large malignant melanoma tumors in mice. In tissue culture, they have destroyed other cancer cell types, including breast and colon.
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The scientists are also exploring the potential use of the new materials as antimicrobial drugs. This application of the chlorophyll derivatives may be particularly important in view of the growing problem of bacterial resistance to antibiotics. A recent study showing that 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.
The development of "green" PDT for clinical use is being funded and will be clinically tested in a year or so by the Dutch company Steba Beheer NV, which has been granted a worldwide license for the product by Yeda Research and Development Co. Ltd., the Weizmann Institute's technology transfer arm.