JULY 15, 2009--According to a new study, light-activated drug delivery technology by PCI Biotech (Oslo, Norway) can significantly slow the growth of invasive tumors in mice. Researchers say the results provide evidence of the clinical potential of photochemical internalization (PCI) in treating human cancer.
The study, published by the journal Photochemistry and Photobiology, is the first to trial the PCI process on an aggressive tumor resembling that of human soft tissue sarcoma (STS). Currently, up to half of all patients newly diagnosed with STS die within five years, and recurrence of tumors after surgery is common. The study indicates that PCI could help to slow or eliminate recurrence of disease by enhancing the delivery of drugs to the tumors.
In previous experiments with the PCI technology, tumors were implanted just under the skin. In the current study, researchers at the Norwegian Radium Hospital used a model where the tumors 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 tumors grew.
When PCI was combined with the cytotoxic drug bleomycin, the tumors 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 (PDT) was used. According to the researchers, PCI produced better treatment effects than PDT because it was more effective at the periphery of the tumor, where a rim of treatment-resistant tumor 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 has been highlighted as a very interesting study on the homepage of the American Society of Photobiology.
According to Dr. Anders Høgset, Chief Scientific Officer of PCI Biotech, "The subsistence of a rim of treatment resistant cells in the tumor 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 tumors can be permanently removed."
PCI Biotech is a Norwegian biopharmaceutical company developing a novel light directed drug delivery system based on its patented photochemical internalization (PCI) technology. Originating from world leading research at the Norwegian Radium Hospital, the PCI method involves first injecting target cells with a photo sensitizer. 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 reportedly 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.
For details on the study, see the paper, Photochemical Internalization of Bleomycin is Superior to Photodynamic Therapy Due to the Therapeutic Effect in the Tumor Periphery, at Photochemistry and Photobiology. See also PCI Biotech's website.