Light-directed drug delivery system slows growth of invasive tumours
PCI Biotech’s photochemical technology shows clinical potential in mouse models
Oslo, 13 July, 2009 – PCI Biotech’s light-activated drug delivery system is able to significantly slow the growth of an invasive tumour in mice, according to a new study. Researchers say the study provides new evidence of the clinical potential of photochemical internalization (PCI) in treating human cancer.
The study is the first to trial the PCI process on an aggressive tumour resembling that of human soft tissue sarcoma (STS). Currently, up to half of all patients newly diagnosed with STS die within five years, with recurrence of tumours after surgery being an important problem. This study indicates that PCI could help to slow or eliminate recurrence of disease, by enhancing the delivery of drugs to the tumours.
In previous experiments with the PCI technology, tumours were implanted just under the skin. In the current study, researchers at the Norwegian Radium Hospital used a model where the tumours grow invasively into the leg muscles of mice to produce a more accurate model of human STS. The mice were treated with different combinations of drug and light therapy whilst researchers measured how fast the tumours grew.
When PCI was combined with the cytotoxic drug bleomycin, the tumours took 27 days to reach the end point of 1000 mm3 compared to 6 days without treatment, 7 days with bleomycin treatment only and 10 days when an ordinary photodynamic therapy was used. According to the researchers, PCI produced better treatment effects than photodynamic therapy because it was more effective at the periphery of the tumour, where a rim of treatment resistant tumour cells remains after PDT treatment,. In addition previous studies have suggested that PCI also has better efficacy in deeper tissue layers.
Drug molecules such as bleomycin are initially taken up by the cell in enclosed compartments or vesicles called endosomes. Unlike other photodynamic approaches, the PCI system uses photosensitizers that localize to the membranes of these vesicles and, when activated by light, cause them to burst. This releases the drug molecules inside the cell, strongly enhancing the effect of the drug.
The study by Dr. Ole-Jacob Norum and co-workers is published in the journal Photochemistry and Photobiology. It has been highlighted as a very interesting study by the American Society of Photobiology on its home page.Dr. Anders Høgset, Chief Scientific Officer of PCI Biotech, comments: “The subsistence of a rim of treatment resistant cells in the tumour periphery is a well-known problem, both after photodynamic therapy and in other cancer treatment modalities. The demonstration in this study that the PCI technology can also target such cells further substantiates the clinical usefulness of the PCI technology. This is one of several studies emphasizing the important contribution from the researchers at The Norwegian Radium Hospital in exploring the potential of the PCI technology, and it will be interesting to see if a further development of the principles described in this study can lead to treatment conditions where even invasive tumours can be permanently removed.”
PCI Biotech is a Norwegian biopharmaceutical company developing a novel light directed drug delivery system based on its patented photochemical internalisation (PCI) technology. Originating from world leading research at the Norwegian Radium Hospital, the PCI method involves first injecting target cells with a photosensitiser. Therapeutic molecules are then delivered to the cells and when these are illuminated the cells' endosomes are ruptured to allow successful delivery of the drug.
PCI can enhance the delivery of all molecules taken into the cell by endocytosis. This includes most types of macromolecules, drugs carried by antibodies or nanoparticles, as well as some small molecule drugs. In addition, PCI can facilitate the use of efficient, but very toxic anti-cancer compounds, by restricting their effects to the target site.
PCI Biotech follows a dual strategy of using its technology to improve the effect both of existing drugs and of emerging treatments such as gene therapy. PCI Biotech's first clinical study combines the proprietary photosensitiser Amphinex® with the cytotoxic agent bleomycin and is scheduled for start in 2009.
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