Is there a 'magic bullet' for cancer?

Scientists are working on a light-activated technique in the battle against cancer, reports Rachel Liddle.

What is the story?
A radical therapy that uses ultraviolet (UV) light to target tumours could be an 'ultra-specific magic bullet' against cancer, according to media reports.

The technique, developed by UK scientists, has cured ovarian cancer in mice and is being touted as a major treatment breakthrough for a range of human cancers.

For the treatment, patients are injected with cancer-fighting antibodies that are rendered inactive with a coating of organic oil. Shining a beam of UV light on to the tumour activates the antibodies in this area, leaving other tissues unaffected. Once activated, the antibodies recruit T-cells to the tumour, allowing the patient's own immune system to kill the tumour.

Antibodies are becoming a big area for cancer treatments. The latest technique could improve therapy with drugs such as Herceptin (trastuzumab), say the papers.

What is the research?
The reports are based on the work of a team from University of Newcastle-upon-Tyne, which has been working out how to improve cancer treatment specificity so it only attacks the cancer, not healthy tissues.

In an attempt to create an 'elegant' alternative to available cancer therapies, the team combined two phenomena: photoactivation of molecules and cancer-fighting antibodies that work by recruiting killer T-cells to tumours.

They 'cloaked' the antibodies with photocleavable 2-nitrophenylethanol (NPE). This left the antibodies able to bind to tumour cells, but rendered the part that binds T-cells inactive.

Irradiation with UVA light then caused NPE groups to fall away from the antibody, and it was able to activate T-cells, as was shown using a lab technique called flow cytometry.

After creating a way of reversibly activating antibodies in response to UVA light, the team next wanted to see if this would also happen when the molecules were in a physiological setting.

They applied the NPE technology to a hamster antibody that acted in a similar way to the human antibody.

Experiments on mice showed that injecting ovarian tumour cells along with the NPE antibody, and then irradiating the mice with UVA, reduced tumour growth so much that five out of six mice had no trace of cancer.

As this effect was greater than that seen when the tumour was injected with antibody without an NPE coating, researchers concluded that their technique added potency to the treatment.

What do the researchers say?
Lead researcher Professor Colin Self said the technique could add a second layer of specificity to emerging antibody treatments.

'The holy grail in this whole area is to make a magic bullet,' he said. 'Magic bullets come down to one thing, that's absolute specificity, which is what we're aiming for here.'

The light-activating technique could be used with a range of therapeutic antibodies that have been raised against cancers, said Professor Self.

Clinical trials of the technique, focusing on secondary tumours in the skin, should go ahead next year, depending on funding.

What do the experts say?
Dr Cat Arney, from Cancer Research UK, said: 'It isn't a treatment that's yet been shown to work in an animal system.'

More research demonstrating that adding cloaked antibodies to target a tumour with light and not affect other tissues, is needed before clinical trials take place.

Other research teams are working on targeted antibody therapies using different approaches, such as radiation, she added. 'It's a variation on a theme that is already being researched.'

Informing patients

  • Scientists are working on a way to activate cancer drugs at the tumour site.
  • This focuses on antibody drugs, which work in the same way as the breast cancer treatment Herceptin.
  • Light-activated treatments could be one way forward.

rachel.liddle@haymarket.com

ChemMedChem 2007; 2: 1,587-90; 1,591-93

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