Cancer gets the 'bullet'

NORTH-EAST scientists have discovered a new light sensitive “magic bullet” treatment for cancer.

NORTH-EAST scientists have discovered a new light sensitive “magic bullet” treatment for cancer which propels the body’s immune system to fight tumours with pin-point accuracy.

The new UV-A light technology method, hailed as a world first, has been developed at Newcastle University where researchers believe it could replace current treatments such as chemotherapy for the most common forms of the disease such as breast, lung, prostate, skin and stomach cancers.

Therapeutic antibodies have long been recognised as having excellent potential in treating cancer but getting them to efficiently target tumour cells has proved to be very difficult.

Now, Professor Colin Self and Dr Stephen Thompson from Newcastle University have developed a procedure which activates antibodies using UV-A light and targets a tumour in a specific area of the body.

Unlike chemotherapy the “gentle” non-invasive treatment does not attack healthy cells so there are little side effects and it is hoped that it could be used alongside conventional treatments such as surgery, chemotherapy and radiotherapy and in the future as the sole therapy for treating cancer.

Newcastle clinical biochemist Professor Self described the development as the equivalent of “ultra-specific magic bullets”.

“A cure for cancer is our vision and this would be a very positive contribution towards that. It will open up a wider use of therapeutic antibodies to provide gentler, safer, more specific therapy for patients.

“This is the ultimate minimally invasive technique which is the way we are moving. It would be wonderful if this gentler treatment could be used as the only method of treatment.”

Antibodies are proteins that play a key role in defending the body against infection. They both neutralise invaders directly, and cause other elements of the immune system to home in on them.

The new system cloaks antibodies with an organic oil which renders them inactive until illuminated by UV rays.

By using a probe to shine light on a tumour, they can be brought to life at that particular site. They in turn cause immune system cells in the blood called T-cells to attack the cancerous tissue. This method causes the immune system to focus on the tumour, recognise that it is not part of the body, and get rid of it. Prof Self has set up a company, BioTransformations Ltd, to develop the technology. He hopes to begin clinical trials with patients suffering from secondary skin cancer early next year which would last three years.

As the antibodies are activated by UV, patients may have to be advised to avoid direct sunlight for a short period after treatment.

He said: “This method could mean that a patient coming in for treatment of bladder cancer would receive an injection of the cloaked antibodies. She would sit in the waiting room for an hour and then come back in for treatment by light. Just a few minutes of the light therapy directed at the region of the tumour would activate the T-cells causing her body’s own immune system to attack the tumour.”

Millions of pounds have been spent over the years on research to develop antibodies which target specific types of cancer cells such as Herceptin for breast cancer.

The challenge has been harder than first expected but by applying the UV-A light method with these antibodies scientists could also target certain types of cancer in a certain region without killing healthy cells.

The implications are far reaching as many antibodies developed by scientists across the globe which are not specific enough to currently use in the battle against cancer could be brought out of storage and used with this method.

“The most exciting part of this is being able to take these other antibodies that other people have taken time, money and effort to create and make them work well enough to be used as front line important therapeutic agents to kill cancer as gently as possible.”

The details are contained in two papers published online today in the journal ChemMedChem.

Josephine Querido, Cancer Research UK senior science information officer, welcomed the breakthrough. “Developing treatments that attack cancer cells but leave healthy tissue unharmed is the holy grail of cancer research. Although at a very early stage, this new approach has potential, and we await the outcome of further research with interest,” she said.

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Immune system fights back: how the treatment works

NEWCASTLE University researchers coat the surface of a protein, such as an antibody, with an organic oil, a process called “cloaking”.

This prevents the antibody reacting within the body unless it is illuminated.

When UV-A light is shone on to the cloaked antibody it is activated.

The activated antibody binds to T-cells, the body’s own defence system, triggering the T-cells to target the surrounding tissue.

When the cloaked antibodies are activated by light near a tumour, the tumour is killed. This work means that antibodies can be targeted to kill cancerous tumours with much greater specificity giving fewer side effects.

In combination with personalised antibodies for certain cancers. These cloaked antibodies can be used alone, or in conjunction with the many antibodies already produced against a wide variety of cancers. It could be used with Herceptin which was produced specifically for breast cancer. A bispecific complex is formed from two antibodies, one binding to a targeted foreign body protein and the other with a T-cell. In this way, T-cells are directed against antibody-tagged proteins, which may be part of a tumour.

The scientists envisage using one of the light-sensitive antibodies for the T-cell half of the complex.

This antibody would remain inert until activated by UV light. As a result, when a bispecific antibody complex binds to healthy tissue away from light, it cannot activate T-cells. Side effects are therefore kept to a minimum.

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