Can cancer drugs that attack B cells (above) also help to treat conditions such as rheumatoid arthritis? Credit: CNRI/SPL

Biotechnology firm Genentech is pinning its hopes on a mouse model, in a bid to broaden the use of a billion-dollar cancer drug.

The company, based in South San Francisco, makes the drug Rituxan, which is used to treat non-Hodgkin's lymphoma. But clinical trials have suggested that the drug may also alleviate symptoms of autoimmune diseases, in which the immune system attacks the body's own cells. To test this idea, the company has created a mouse model that it says could speed up research on such diseases.

Rituxan works by targeting a specific protein carried on the surface of B cells, which form part of the body's immune response. By latching on to these cells it marks them for destruction, in the process clearing cancerous cells from the body. Genentech's new mouse model expresses the human B-cell protein recognized by Rituxan.

The model was announced on 19 April by Andrew Chan, Genentech's vice-president for immunology research, at the Federation of American Societies for Experimental Biology meeting in Washington DC. Scientists say that it could help fill a need for research on whether ‘depletion therapies’, such as Rituxan, can safely help patients with autoimmune diseases, by lending insight into the drugs' action. So far, many such therapies have yielded disappointing results in the clinic, but researchers hope that the new model could help to break that pattern.

“The preclinical models for depletion were really centred around cancer,” says Edward Clark, an immunologist at the University of Washington in Seattle. “We need good preclinical models to study these treatments in autoimmune diseases as well.”

Chan told the meeting that the model has already been used to investigate key safety issues. For instance, clinical trials suggest that Rituxan eases symptoms of the autoimmune disease rheumatoid arthritis, in which the body destroys its own joints. But scientists had been puzzled by the fact that Rituxan does not seem to cause serious infections in the arthritis sufferers, even though it depletes their immune system of B cells.

Genentech scientists found that in mice some types of B cells survived the Rituxan treatment. Chan and his co-workers speculate that the drug kills only certain classes of B cell, leaving others behind to fight off disease. “Maybe this is why the arthritis patients keep fairly intact immune systems,” Chan says.

The finding might also have implications for how long and how well the drug works. Genentech is investigating such issues in a large clinical trial of Rituxan in rheumatoid arthritis patients. It is also testing Rituxan in patients with another autoimmune disease, called systemic lupus erythematosus.

Like many autoimmune diseases, lupus is poorly understood and difficult to treat. Clark, who has worked as a paid consultant to Genentech in the past, says that the new model could help answer questions that have held back this research, such as why depletion therapies only work in some autoimmune diseases, and whether the drugs can be made to work better.