FROM LOCAL TO SYSTEMIC CANCER THERAPY WITH BACTERIOCHLOROPHYLL DERIVATIVES AND LIGHT

Avigdor Scherz, Plant and environmental sciences, Weizmann Institute of Science, Rehovot, Israel

The emerging paradigm of “Tumors as organs” motivates a shift in cancer treatment strategies. We have learned from Nature that Hypersensitive response in plants, sepsis and ischemia-reperfusion injury in animals and humans often ends in organ collapse through in-situ cogeneration of oxygen and nitric oxide radicals. We therefore hypothesized that simultaneous production of these radicals in the tumor circulation should ignite vascular pathology leading to irreversible tumor collapse. We are now able to generate such radicals in the tumor circulation by near infra-red excitation of novel derivatives of the photosynthetic pigment bacteriochlorophyll (Bchl). The new treatment approach called Vascular Targeted Photodynamic Therapy  (VTP) enables irreversible tumor collapse through coagulative necrosis as was demonstrated in both animals and humans.  In recent animal studies this process was shown to expose tumor associated antigens and dangerous associated molecular pattern and thereby provoke ant-tumor immune response. Modulation of the immune system by different agents synchronized with VTP leads to regression of micrometastases and high cure rate in several animal models.  Successful Phase II trials in Europe and the US led to Phase III clinical trial of VTP using WST11, a water soluble derivative of Pd-Bchl,  that are close to conclusion in >60 European and South American centers. New research and clinical trials in collaboration with Memorial Sloan Kettering Cancer Center in NY, US, are currently undertaken  aiming to test the possible treatment of prostate cancer and other indications in the more advanced stage (e.g. metastatic) by combining VTP with immune modulation.

Supported by Steba Biotech, France; The Wade Thompson Foundation, USA