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Two are better than one

Cancer patients may one day benefit from treatment with mixtures of customized antibodies. In a study published recently in the Proceedings of the National Academy of Sciences (USA), a team of Weizmann Institute scientists have demonstrated how the right combination might form a web that destroys the cancer cell's communication network, ultimately demobilizing the cell.

Three decades of intensive cancer research led to the identification of a family of receptors, known as HER, that sit antenna-like on the outside of the cell wall and are implicated in certain types of cancer. A team of researchers under Prof. Yosef Yarden, Dean of the Weizmann Institute's Feinberg Graduate School and a professor in the Institute's Biological Regulation Department, had previously found that, under certain conditions, the HER2 receptor amplifies the growth signal received by the cell. Yarden and Prof. Michael Sela, former president of the Weizmann Institute of Science, and currently a professor in the Institute's Immunology Department, teamed up to create a strategy for the customization of antibodies that work independently to engage these cancer-specific receptors and shut down the attendant signaling network. The study was carried out in cooperation with researchers from Targeted Molecular Diagnostics, Westmont, IL, USA.

In experiments conducted in vitro and in lab mice, the researchers exposed the cancer cells to two different antibodies that link up to HER2 receptors. In a synergistic action, the antibodies were shown to cooperate rather than compete for distinctly different attachment points on the architecture of the receptors, resulting in the assembly of a large, springy molecular scaffolding between the receptor towers. The interlocking system grips and pulls the receptors towards each other until they collapse inward like overloaded laundry lines. The stressed receptors become engulfed by the cell, and thus cease signaling. In response, the cell halts growth
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Source:Weizmann Institute


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