Using Antibodies to Override Immune Checkpoints and Brakes in Cancer Therapy

Targets now include cytotoxic T cells, Natural Killer cells, and immune-suppressing cells.

Many of the most exciting new anti-cancer drugs are antibodies that target the immune system. The goal is to turn on the body’s natural defenses against abnormal cells. Several new drugs override the immune system’s natural regulatory processes; the processes that prevent our immune system from attacking normal cells and causing autoimmune disease or tissue destruction.

Because too much immune activity is destructive to tissues, the body has multiple layers of regulation, which can be simply viewed as accelerators or brakes. The accelerators promote cytotoxic and inflammatory immune responses; the brakes suppress these responses.

Cytotoxic T cells are also referred to as effector T cells. In some cases, these cells can recognize cancer cells. However, the cancer cells can avoid destruction by displaying proteins that engage the immune checkpoints on cytotoxic T cells. Alternatively, interactions with other immune cells in the tumor environment can keep the cytotoxic T cells in an inactive state. The primary targets for ICIs are the interacting proteins that keep cytotoxic T cells in an inactive state or prevent the cytotoxic T cells from attacking cancer cells.

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