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Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints , key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus.
This checkpoint is the target of Merck & Co.'s melanoma drug Keytruda, which gained FDA approval in September 2014. The checkpoint is also the target of EMD Serono (Merck KGaA)'s drug Bavencio, which gained FDA approval in 2017. An advantage of targeting PD-1 is that it can restore immune function in the tumor microenvironment.
The prevalence of checkpoint inhibitor induced colitis varies depending on the regimen of immunotherapy. The incidence is 0.7 – 1.6% for anti- programmed cell death protein 1 (PD1) agents, 5.7 – 9.1% for anti- cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and about 13.6% for combination therapy. [ 2 ]
The interaction of these cell surface proteins is involved in the suppression of the immune system and occurs following infection to limit the killing of bystander host cells and prevent autoimmune disease. [2] This immune checkpoint is also active in pregnancy, [3] following tissue allografts, [4] and in different types of cancer. [5]
CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers. [5]
Eftilagimod alpha (INN; [1] development code IMP321 or efti) is a large-molecule cancer drug being developed by the clinical-stage biotechnology company Immutep.Efti is a soluble version of the immune checkpoint molecule LAG-3.
A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, [1] is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2), thereby interfering with the JAK-STAT signaling pathway in lymphocytes.
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