Photochemical Internalization Cancer Treatment with Minor Side Effects Closer to Reality

A Norwegian biotech company is getting closer to creating a treatment that destroys only cancer cells, leaving other cells unaffected.

It is not hard to find a drug that destroys cancer cells. The problem lies in the fact that a drug’s active compounds kill indiscriminately, not only diseased cells die but also other cells in the body. This is why the side effects associated with conventional cancer treatment are frequently so severe.

The hope of any cancer researcher is to develop a drug that works only against a cancerous tumor--without adversely affecting the rest of the body. This objective can be attained in two ways: one is to produce targeted drugs that affect only the cancer cells; the other is to design smarter way of delivering a drug to its target without affecting other parts of the body.

A biotech company, PCI Biotech Holding, ASA (Lysaker, Norway), has been focusing on the latter approach since 2000. Researchers working on the project Fotokjemisk internalisering for Cellegiftterapi av Kreft (Photochemical Internalization of Chemotherapy) have steadily been getting closer to a solution. Headed by chief scientific officer Dr. Anders Høgset, the project has received funding under the Program for User-driven Research-based Innovation (BIA) at the Research Council of Norway.

The technology is based on light and is called photochemical internalization (PCI). It was discovered in 1994 at the Norwegian Radium Hospital in Oslo (now part of Oslo University Hospital). 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 significantly 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 photosensitizing compound,” explained Dr. Høgset. “This is a chemical substance increasing cells’ sensitivity to light. We have created and patented a molecule [Amphinex] that 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 tumor 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.”

The challenge of effectively transporting molecules to a targeted area inside a cell has long stumped cancer researchers. For pharmaceutical companies, it has created a logjam, slowing down further development of a number of molecules with great therapeutic possibilities.

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

These cancer-killing medications pass through cancer cell membranes much more easily, which considerably 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,” explained Dr. Høgset.

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 tumors disappeared altogether. No serious side effects were observed,” said Dr. Høgset.

PCI Biotech is now going to follow-up with additional clinical research. Up to the present, PCI Biotech has focused on localized cancer treatment, for example, for mouth cancer, breast cancer, and facial skin cancer. Many cancer patients stand to benefit greatly from localized treatment, but a great number also require treatment that can attack cancer that has metastasized to other areas of the body.

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

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