Immune-checkpoint blockade is a form of immunotherapy, meaning it aims to help the patient’s own immune system fight cancer. It uses substances called monoclonal antibodies, which are designed by drug companies to target extremely specific molecules on cell surfaces. In this case, the antibodies unblock a reaction that stops the immune system’s natural attack on invading cancer cells.
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The checkpoint inhibitors may also have uses in battling some chronic infections. Trials using the antibodies against
hepatitis B,
HIV and even the
blood infections that contributes to 200,000 U.S. deaths each year are underway or in planning stages.
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How they work
One way our bodies deal with infections, and with cancer is by activating immune cells, called T-cells, which recognize foreign agents and marshal various parts of the immune system to clear or control them. Certain types of T-cells infiltrate tumors and release chemical signals that tell other parts of the immune system to attack. But one of these signals, a chemical called interferon-gamma, tells tumor cells to produce a molecule that actually blocks the T-cell response.
This inactivation switch probably evolved to keep our immune systems from going haywire — overreacting and damaging organs. In dealing with cancer, however, the mechanism is a Catch-22, because it allows the cancer to grow.
So in the mid-1990s, scientists began designing
monoclonal antibodies to short-circuit the immune switch-off. Most of the checkpoint inhibitors under development target a protein on T-cells that scientists in 1992 named “Programmed Death Receptor 1” (at the time they knew only of its role in the natural death process of cells); it is now called PD-1. Other monoclonal antibodies target a tumor molecule that binds with PD-1 and is called PD-L1. This molecule appears only on the surface of certain tumor cells when they are under attack from T-cells; interferon-gamma causes it to appear.
