Why Immune Checkpoint Inhibitors Represent a Breakthrough

Immunotherapy has been in used for decades via treatments that activate the immune system to attack and destroy cancer cells. For an overview of immunological treatment strategies in clinical studies for cancer patients see Tables 1a and 1b. One limitation of this approach has been that certain cell interactions involving immune “checkpoints” automatically dampen the activated immune system to avoid autoimmunity. So, “when you stimulate [the immune system], you also put on the brakes.”* Meanwhile, cancer cells are fiendishly good at mutating, adapting, and avoiding detection by the body’s natural radar, and the effectiveness of immunotherapy often wanes over time. In some tumor types, these hurdles appear to be overcome by the newest class of drugs targeting the immune system: immune checkpoint-blocking antibodies, or immune checkpoint inhibitors (ICIs). ICIs block the pathways on T-cells that inhibit immune response. In other words, they release the brake pedal and allow the immune system to remain activated, often producing a strong and sustained anti-tumor response. (T-cells are regulator cells that orchestrate the immune response against infections or cancer cells.) *Ribas, Antoni quoted by Malini Guha in “The New Era of Checkpoint Inhibitors” The Pharmaceutical Journal.

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