Laser microscopy reveals cancer drug's killing power

Scientists from the Manchester Collaborative Centre for Inflammation Research at the University of Manchester (MCCIR; Manchester, England), using laser microscopy, have discovered why a particular cancer drug is so effective at killing cells. Their findings could be used to aid the design of future cancer treatments.

Related: Laser techniques part of $24M European drug discovery project

Professor Daniel Davis and his team used laser-based microscopes to produce videos of the process by which the drug rituximab binds to a diseased cell and then attracts white blood cells known as natural killer (NK) cells to attack. (Rituximab is widely used in the treatment of B cell malignancies, such as lymphoma and leukemia, as well as in autoimmune diseases like rheumatoid arthritis.) They discovered that rituximab tended to stick to one side of the cancer cell, forming a cap and drawing a number of proteins over to that side. It effectively created a front and back to the cell, with a cluster of protein molecules massed on one side.

But what surprised the scientists most was how this changed the effectiveness of NK cells in destroying these diseased cells. When the NK cell latched onto the rituximab cap on the B cell, it had an 80% success rate at killing the cell. In contrast, when the B cell lacked this cluster of proteins on one side, it was killed only 40% of the time.

"What our findings demonstrate is that this ability to polarize a cell by moving proteins within it should be taken into consideration when new antibodies are being tested as potential treatments for cancer cells," explains Davis. "It appears that they can be up to twice as effective if they bind to a cell and reorganize it."

Much of the research for this study was carried out during Davis’ time at Imperial College London. He will be continuing to use video imaging at a microscopic level to investigate immunology at the MCCIR.

The research was carried out in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, and funding for the work came from the Medical Research Council.

Full details of the work appear in the journal Blood; for more information, please visit http://bloodjournal.hematologylibrary.org/content/early/2013/04/23/blood-2013-02-482570.

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