LONDON - Antisoma plc said it made important progress in the preclinical development of its targeted apoptosis program, demonstrating for the first time that its construct can kill breast cancer cells in culture.

The construct consists of a tumor-targeting monoclonal antibody linked to the enzyme DNase, which triggers apoptosis. Earlier this year the company, based in London, said it succeeded in producing a fused protein that exhibited both DNase activity and the ability to recognize cancer cells. Last week, Agamemnon Epenetos, chief scientific officer, presented data at the American Association for Cancer Research meeting in San Francisco showing that the fusion proteins can target and kill breast cancer cells in tissue culture.

"The Holy Grail in cancer therapy is to have a product that is non-toxic while it circulates in the bloodstream, but which will home in on the tumor and cause just the cancer cells to die naturally," Epenetos said.

Even if they are targeted only to the tumor, many chemotherapeutics are so aggressive that the death of the cancer cells provokes life-threatening severe inflammatory reactions.

"We believe we have developed a way to push the cancer cell toward choosing to commit suicide," he said. "In this case, the cell breaks down naturally and the body's natural mechanism sweeps up the debris."

HMFG1, the humanized monoclonal antibody used by Antisoma, targets polymorphic epithelial mucin on the tumor cell. It is capable of homing in on most epithelial cancers, including breast, lung, colorectal, pancreatic, prostate, ovarian and gastric.

Work now is under way in collaboration with the antibody manufacturer, Lonza Biologics, to scale up production of the molecules. Antisoma aims to complete preclinical studies and enter human trials in 2001.

The technology was licensed from the charity, the Imperial Cancer Research Fund. Antisoma has a similar project with the U.S. National Cancer Institute in the area of using RNase to initiate apoptosis. A U.S. and European patent covering such fusion molecules has been granted.

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