Professor Dan Davis and his team at the MCCIR have discovered why the cancer drug rituximab kills cancerous B cells so effectively. The drug is widely used in the treatment of B cell malignancies such as lymphoma and leukaemia, as well as with autoimmune diseases such as rheumatoid arthritis. The findings could be integral to the design of future cancer treatments.
Using high-powered laser based microscopes, researchers made videos of the process by which rituximab binds to a diseased cell and then attracts white blood cells, known as natural killer (NK) cells, to attack. They discovered that rituximab tended to stick to one side of the cancer cell, forming a cap and drawing a number of proteins to that side. Effectively, it caused a front and back to the cell – with a cluster of protein molecules on one side.
What most surprised the scientists was how this changed the effectiveness of NK cells. When NK cells latched onto a rituximab cap which had already drawn a protein cluster to one side of the cell, it killed the cell 80% of the time. Without the cluster of proteins, it killed only 40% of the time. Professor Davis said:
“These results were unexpected. It was only possible for us to unravel why this drug was so effective through the use of video microscopy. Watching what happened within the cells, we could identify why rituximab is so effective. It tended to reorganise the cancerous cell, making it especially prone to being killed. Our findings demonstrate that the ability to polarise a cell by moving proteins should be considered when new antibodies are tested as potential cancer treatments. It appears they can be twice as effective if they bind to a cell and reorganise it.”
Dr Matt Sleeman, Senior Director of Biology at MedImmune, said:
“This great observation can influence how we as a biotech company identify and design future therapies. It shows how innovative thinking can be achieved by working with top academics. I am excited by the potential of the MCCIR to bring further innovation and ultimately bring benefits to patients. ”