Immune checkpoint


Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets.
Inhibitory checkpoint molecules are targets for cancer immunotherapy due to their potential for use in multiple types of cancers. Currently approved checkpoint inhibitors block CTLA4 and PD-1 and PD-L1. For the related basic science discoveries, James P. Allison and Tasuku Honjo won the Tang Prize in Biopharmaceutical Science and the Nobel Prize in Physiology or Medicine in 2018.

Stimulatory checkpoint molecules

Four stimulatory checkpoint molecules are members of the tumor necrosis factor receptor superfamily—CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belongs to the B7-CD28 superfamily—CD28 itself and ICOS.
Drugs or drug candidates that inhibit/block the inhibitory checkpoint molecules are sometimes known as checkpoint inhibitors; this idea is often referred to as immune checkpoint blockade, or simply checkpoint blockade. Checkpoint inhibitor drugs have seen growth in pharmaceutical research in cancer by companies including Bristol-Myers Squibb, Merck, Merck KGaA, Roche and AstraZeneca. A new area of checkpoint inhibitor drugs is being pursued by Palleon Pharmaceuticals, who are working on inhibiting SIGLEC 7 and SIGLEC 9 as a new class of receptors for antibody therapeutics.