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Photodynamic Therapy (PDT) & Cancer

PhotoBiotics' uniquely targeted approach to the use of photodynamic therapy for cancer and other diseases represents a major advance in therapeutic possibilities. However, the history of using light to treat disease is a long one. Records show that the curative combination of light and dyes was known to the ancient Egyptians: they used an extract of sorrel in conjunction with sunlight to relieve skin complaints. But understanding that light, in the form of a cold laser directed at photosensitising drugs (dyes) in diseased tissues, could convert nearby oxygen into a highly toxic form called 'singlet oxygen' that destroys any cells in close proximity only arrived in the second half of the 20th century. This combination of light and photosensitisers – photodynamic therapy or PDT - was fully realised in 1976, with the first successful trials of a PDT drug in human volunteers. In January 1998, Photofrin (porfimer sodium, marketed by Quadralogics Technologies, QLT, based in Vancouver, Canada) was the first photosensitiser to be approved for use in the photodynamic therapy of cancer.

To date, PDT has successfully established a niche in the treatment of certain cancers (e.g., those of head and neck and skin), and in age related macular degeneration (AMD - a common cause of visual impairment in the over-50’s). Compared to other treatments, photodynamic therapy for cancer leaves little cosmetic scarring and, in contrast to chemotherapy, has no possibility of drug resistance.

Though in some ways a successful PDT drug, Photofrin suffers from a number of shortcomings:

• It is a difficult–to-reproduce mixture of compounds (some of which are PDT inactive);
• It lacks specific targeting to diseased tissues
• It clears slowly from the system (leading to patients being acutely photosensitive for some time after treatment, causing symptoms akin to acute sunburn in uncovered parts of the body)
• It is poor at producing singlet oxygen
• It absorbs strongly in the blue region of the visible spectrum, and blue light has little skin penetration, which limits Photofrin’s use to conditions on or near external and internal bodily surfaces easily accessed by a light source.

'Second generation' photosensitisers for PdT and cancer and other diseases

So-called 'second generation' PDT photosensitisers have been developed with much improved singlet oxygen production. The most successful of these to date has been verteporfin, developed by QLT and marketed by Novartis as Visudyne for the treatment of AMD. The earlier market success of this drug was shown by its annual sales of around half a billion dollars a year. Verteporfin works by targeting leaking proliferating blood vessels in the cornea that give rise to the AMD condition. After injection, the drug is allowed to equilibrate in the eye, and then the cornea is irradiated through the iris with a cold red laser.

Another useful drug, especially for photodynamic therapy of cancers in thehead and neck, is Foscan (temoporfin). Originally developed by Scotia Pharmaceuticals, Foscan has excellent singlet oxygen production, but suffered from poorly organised clinical trials that led to its non-acceptance by the FDA and initially by the EMEA. This in turn led to Scotia’s demise and an unfortunate market slur on PDT’s good name. However, Foscan was acquired by Biolitec and is now being marketed in Europe for head and neck cancers, where it is reimbursed in most territories, at €7,000 per treatment unit.

Though other 'second generation' PDT sensitisers are coming to market or are in various stages of Phase II and Phase III trials for a variety of conditions, none is truly targeted.

PhotoBiotics' unique targeted approach to photodynamic therapy for cancer

For PDT to reach its full therapeutic potential in cancer and other indications, it is important to improve the photophysics and specific targeting of current photosensitisers. PhotoBiotics has achieved both these goals by:-

• Using antibody fragments to target multiple photosensitiser molecules directly to diseased tissues

• Creating new more soluble photosensitisers capable of activation at longer light wavelengths, ensuring light penetrates more deeply into diseased tissues

The result is that PhotoBiotics' uniquely targeted approach to photodynamic therapy for cancer greatly improves PDT’s therapeutic margin, while drastically reducing photosensitivity. This means PDT will be more effective and better tolerated in a wider range of cancers, AMD, microbial infections, restenosis following angioplasty, and various proliferative skin conditions. It will also enable the targeting of imaging agents, so improving tumour detection.