Antibody 'Puts Immune System in Overdrive'
By Celia Hall

The experimental drug that has caused the violent reaction in six healthy volunteers is an entirely new type of antibody treatment which puts the body's immune response into overdrive rather than subduing it. That may help to explain why the reaction was so severe. The antibody also stays in circulation for a long time, making it very hard for doctors to treat the young men affected.

Prof Sir Gregory Winter, a world leader in antibody research, said that the new antibody "super-charges" the immune response in the body rather than turning it down. "Other antibody drugs like Herceptin (for breast cancer), Avastin (for bowel cancer) or Humira (rheumatoid arthritis), for example, appear to be relatively safe but these basically turn a response down."

The drug, called TGN1412, is an antibody treatment designed for some forms of leukaemia and rheumatoid arthritis. It stimulates the production of T-cells with the aim of improving control of a malfunctioning immune system.

"This is a different sort of antibody and I don't know of another antibody that is on the market that works in the same way," Sir Gregory said. "It is a different and very potent process and very difficult to predict in advance how mild or severe the clinical response might be."

Sir Gregory is the joint head of the Medical Research Council's laboratory of molecular biology division of protein and nucleic acid chemistry, at Cambridge. He said that the immune system was extremely complex and naturally had a series of checks and balances.

The new drug turned on a molecule called CD28 which helps to activate the T-cells. "You need to be very careful to be sure that you activate the response by just the right amount. You are on a knife edge: too much and it will attack not just the cells you want to attack but many other cells in the body. Furthermore, because the antibody remains in circulation for a long time the response is difficult to turn off."

Camilo Colaco, the chief scientific officer of the specialist immunology company Immunobiology Ltd, in Cambridge, believes that the disaster may expose the shortcomings of pre-clinical testing on mice and other animals. He told Science Business online: "The more we learn about the immune system, the more we realise that the mouse is not a good model for humans. This mismatch may be a particular problem with CD28, where there is little or no cross reactivity between a human antibody and the mouse immune system."

Scientists were also concerned about the effect on research.

Prof Chris Higgins, the director of the Medical Research Council clinical sciences centre, said: "Many antibody therapies treat and cure thousands of patients across the world. It would be a disaster if this one very serious incident impeded the development of new antibody therapies for serious diseases such as arthritis and cancer."

Karol Sikora, professor of cancer medicine at Imperial College, said that monoclonal antibodies were very powerful selective tools aimed at specific proteins on the surface of cells.
"They have been used extensively as treatments for cancer and they can target specific cells that regulate the immune response."
The Daily Telegraph, 17th March 2006

PHILLIP DAY'S COMMENT: The old cry of 'We must have drug trials so that diseases like cancer can be beaten' is, of cause, bankrupt. Nutrition has been curing cancer for years and, in spite of all said, intends to do so for the future. No, we must have drug trials so that the pharmaceutical industry can continue peddling its dangerous, quack remedies to a public slowly stirring itself to the issues. The unfortunate six, I suspect, are the tip of an iceberg that generally goes unreported - well-intentioned human guinea-pigs doing their bit for humanity, who end up with problems for years afterwards for want of a cheque.

Look, if you're that hard up for a few quid ….