Aug 29, 2016
Immune checkpoints are defined as the stimulatory or co-stimulatory molecules involved in the immune system. There are two kinds of checkpoint proteins found on T cells such as PD-1/PD-L1 and cytotoxic T lymphocytes (CTLA-4). The PD1/PD-L1 pathway is an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous anti-tumor activity. PD-1, a protein present in humans encoded by the PDCD1 gene, binds to two ligands- PD-L1 and PD-L2 to prevent the activation of T-cells by regulating the immune system. PD-L1 is a protein present in human encoded by CD274 gene that reduces the proliferation of CD8+ T cells at the lymph nodes by binding to PD-1 or B7.
Immune checkpoint inhibitors are type of drugs, usually antibodies, which block these proteins of the immune system cells. Inhibiting the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor leads to killing of tumor cells by T Cells. PD-1 and PD-L1 inhibitors are used as immunotherapy for treating various cancers such as Lung Cancer, Metastatic Renal Cell Carcinoma, Head and Neck Cancer and Melanoma. They also protect against immune-mediated tissue damage.
PD-1 and PD-L1 inhibitors have replaced existing chemotherapy and radiotherapy for treating cancer. Several clinical trials for combination therapy of PD-1 and PD-L1 inhibitors are ongoingwith around 245 active clinical studies. The Pipeline of PD-1 and PD-L1 is profuse with approx. 47 drugs with 35 companies involved, including big pharmaceutical companies such as Hoffmann-La Roche, Merck Sharp & Dohme Corp., Pfizer Inc., Bristol-Myers Squibb and AstraZeneca.
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Insight by:
Diksha Wadhwa
Associate Analyst
DelveInsight Buisness Research, LLP
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