How Iplumatinib Works at a Cellular Level

As part of the body’s defense against autoimmunity, a protein called CTLA-4 prevents the immune system’s T cells from attacking the body’s own cells. In the case of cancer, though, that’s a problem. Once he pinpointed CTLA-4 as the T cells’ brake system, Jim Allison worked with a pharmaceutical company to develop an antibody that blocks the protein and releases the brake.

The right side of the image shows normal conditions: a T cell sits above a B cell lymphoma cell. On the left side, the cells come in closer contact, causing rearrangement of CTLA-4 (red) and the T cell’s microtubules (green). The shift, and signals that pass between the cells, stops the T cells from attacking. A drug based on an antibody to CTLA-4—ipilimumab—blocks this interaction, thereby enhancing T cell action. Clinical trials are testing the effectiveness of ipilimumab in treating melanoma.

Image courtesy of the Allison Lab.

-- Amy Maxmen
HHMI Bulletin, November 2010

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