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Cancer Cell Killers Revealed by Laser Microscopy

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MANCHESTER, England, April 24, 2013 — A laser-based microscope video imaging technique has revealed why a particular cancer drug is so effective at killing cells. The findings could revolutionize the design of future cancer treatments.

Using high-quality video imaging, researchers from the Manchester Collaborative Centre for Inflammation Research (MCCIR) captured the process in which rituximab — a drug widely used to treat B cell malignancies such as lymphoma, leukemia and rheumatoid arthritis — binds to a diseased cell, then attracts white blood cells known as natural killer cells to attack.

The investigators found 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. The drug effectively created a front and back to the cell — with a cluster of protein molecules massed on one side.

An image showing cancerous B cells that have been treated with rituximab. The protein CD20 (shown in green) has been drawn to the side of the cells. When the natural killer white blood cells approach, they will stand an 80 percent chance of killing the cell if they latch onto the side where the protein has collected. Courtesy of MCCIR.

But what surprised the scientists most was how this changed the effectiveness of natural killer cells in destroying diseased cells. When the killer cell latched onto the rituximab cap on the B cell, it had an 80 percent success rate at killing the cell; when the B cell lacked this cluster of proteins, however, it was killed only 40 percent of the time.

“These results were really unexpected,” said professor Daniel Davis. “It was only possible for us to unravel the mystery of why this drug was so effective through the use of video microscopy. By watching what happened within the cells, we could clearly identify just why rituximab is such an effective drug — because it tended to reorganize the cancerous cell and make it especially prone to being killed.”

He said that this ability to polarize cells by moving proteins within it should be considered when testing new cancer treatment drugs. “It appears that they can be up to twice as effective if they bind to a cell and reorganize it.”

Most of the research — done in collaboration with MedImmune, the global biologics R&D arm of AstraZeneca — was completed while Davis was at Imperial College London.

He plans to continue using high-quality video imaging at a microscopic level to investigate immunology at MCCI, a collaboration between the University of Manchester, GlaxoSmithKline and AstraZeneca.

The research was supported by the Medical Research Council and appeared in Blood (doi: 10.1182/blood-2013-02-482570).  

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Apr 2013
laser microscopy
Technique using functional optical microscope with the addition of a coherent source collinear with the image path. The laser light is intended to scan the sampled plane and acquire information from fluorescence of the observed ample. Confocal laser microscopy uses this technique.
AstraZenecaBiophotonicscancer treatmentcancerous B cellsDaniel DavisEnglandEuropeGlaxoSmithKlineimaginglaser microscopyleukemialymphomaManchester Collaborative Centre for Inflammation ResearchMedical Research CouncilMicroscopynatural killer cellsResearch & Technologyrheumatoid arthritisrituximabrituximab capUniversity of Manchestervideo imaginglasers

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