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Cancer treatment with minor side effects

It is not difficult to find a drug that destroys cancer cells. The problem lies in the fact that a drug’s active substances kill not only diseased cells but also other cells in the body. This is why the side effects accompanying traditional cancer treatment are often so severe.

Trying to eliminate side effects

(Illustration: Shutterstock) Side effects of traditional cancer treatment are often severe. (Illustration: Shutterstock) The dream of any cancer researcher is to come up with a medication that works solely against a cancerous tumour – without adversely affecting the rest of the body.

This goal can be attained in two ways: one is to produce targeted drugs that affect only the cancer cells; the other is to devise smarter means of delivering a drug to its target without affecting other parts of the body.

A Norwegian company, PCI Biotech Holding ASA (PCI Biotech), has been focusing on the latter approach since 2000. Researchers working on the project “Fotokjemisk internalisering for cellegiftterapi av kreft” (Photochemical internalisation of chemotherapy) have steadily been getting closer to a solution. Headed by Chief Scientific Officer Anders Høgset, the project has received funding under the Programme for User-driven Research-based Innovation (BIA) at the Research Council of Norway.

Laser light and light-sensitive cells

The technology in use is based on light and is called photochemical internalisation or PCI. It was discovered in 1994 at the Norwegian Radium Hospital in Oslo (now part of Oslo University Hospital).

(Illustration: PCI Biotech) Illumination activates the photosensitiser in the membrane of endosomes in the cancer cell, inside which the drug is encapsulated (D). In this way, the membrane is destroyed and the drug is released. (Illustration: PCI Biotech) PCI Biotech uses the technology to direct a red laser to the area of the body where the drug is to have its effect. The light dramatically enhances drug delivery to specific locations inside the diseased cells.

“But in order to achieve the desired effect from the light, we need to give the patient a photosensitising compound,” explains Dr Høgset.

“This is a chemical substance increasing cells’ sensitivity to light. We have created and patented a molecule (called Amphinex®) which we inject into a patient and let circulate for a few days. Then we give the patient the desired drug. After a short while, we shine the laser on the tumour where both Amphinex® and the medication are now present. When light is applied, Amphinex® triggers processes within the cancer cells, substantially enhancing the effect of the drug.”

Reducing doses

The challenge of effectively transporting molecules to a targeted area inside a cell has long stymied cancer researchers. For pharmaceutical companies, it has created a bottleneck, slowing down further development of a number of molecules with great medicinal potential.

Patients have often had to receive higher doses of a drug than what would otherwise be necessary had there existed a way to target drug delivery to the right location inside a cell. Because of these higher doses, the side effects patients experience are commensurately more severe.

(Photo: Pål K. Selbo/PCI Biotech Light-sensitive molecules (orange) before and after photochemical internalisation (PCI) treatment. At left, the molecules are trapped within membranes inside the cancer cell. At right, the molecules have been released and can spread – along with the cytotoxic drugs – throughout the entire cancer cell. (Photo: Pål K. Selbo/PCI Biotech)

“Now we have finally succeeded in finding a way to deliver cancer medications inside the malignant cells, destroying them effectively,” states Dr Høgset.

These cancer-killing medications pass through cancer cell membranes far more easily, which significantly increases their accuracy. It follows that doses can be reduced substantially with side effects becoming correspondingly less severe.
“In the laboratory, we have managed to enhance the effect of some cytotoxic drugs by a full 50 times! We did so by administering Amphinex® and directing light to the cancer cell,” explains Dr Høgset.

The cancer disappeared

PCI Biotech, together with University College London Hospital, began performing research on human subjects two years ago.

“All patients involved in the study experienced a considerable effect from the light treatment and, in most cases, the treated tumours disappeared altogether. No serious side effects were observed,” says Dr Høgset.

PCI Biotech is now going to follow up with further clinical studies.

(Photo: PCI Biotech) PCI treatment of mice: the malignant tumour disappeared entirely in the course of 60 days. (Photo: PCI Biotech)

Tapping into the body’s own immune system

Up to the present, PCI Biotech has focused on localised cancer treatment, for example for mouth cancer, facial skin cancer and breast cancer.

Many cancer patients stand to benefit greatly from localised treatment, but a great number also require treatment that can attack cancer that has spread to other parts of the body.

As part of a future project, PCI Biotech intends to extend its method to treatment of metastatic cancer. The project will investigate whether the technology can activate a person’s immune system, enabling it to attack cancer cells in more than one part of the body.

Project facts

Project title: Fotokjemisk internalisering for cellegiftterapi av kreft (“Photochemical internalisation of chemotherapy”)

Project period: 1 June 2007-31 December 2010

Participants: PCI Biotech, University College London Hospital, Oslo University Hospital, Norwegian Radium Hospital, Synthetica AS, University of Oslo’s School of Pharmacy

Allocation from the BIA programme: NOK 8.5 million

 

 

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