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Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. [5] LAG3, which was discovered in 1990 [6] and was designated CD223 (cluster of differentiation 223) after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, [7] is a cell surface molecule with diverse biological effects on T cell function but overall has an immune ...
Cancer Therapy by Inhibition of Negative Immune Regulation (CTLA4, PD1) A2AR & A2BR: The Adenosine A2A receptor is regarded as an important checkpoint in cancer therapy because adenosine in the immune microenvironment, leading to the activation of the A2a receptor, is negative immune feedback loop and the tumor microenvironment has relatively high concentrations of adenosine. [27]
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.
Lymphocyte Activation Gene 3 (LAG3), an inhibitory (checkpoint) receptor on immune system T-cells. LAG3 is the target of early-stage drugs for cancer and autoimmune disorders; IMP321 is a soluble version of LAG3, developed by Prima, while BMS-986016 (from Bristol Myers) and GSK2831781 (Glaxo) are anti-LAG3 monoclonal antibodies. CD224
The receptor is an immune checkpoint and together with other inhibitory receptors including programmed cell death protein 1 (PD-1) and lymphocyte activation gene 3 protein (LAG3) mediate the CD8+ T-cell exhaustion in terms of proliferation and secretion of cytokines such as TNF-alpha, IFN-gamma and IL-2.
IMP731 is a depleting antibody for autoimmune disease that targets LAG3+ activated T cells. GSK licensed the rights to develop such antibodies from Immutep in December 2010 in a total deal package worth £64m. GSK subsequently developed GSK2831781, its own depleting anti-LAG-3 antibody based on Immutep's original IMP731 antibody. [15]
PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer.
GSK2831781 originated from a chimeric monoclonal antibody to LAG-3 developed in 2008 by the French biotechnology company Immutep. That company had been built around drugs targeting LAG-3 and was associated with Frédéric Triebel, an immunologist generally regarded as a leading authority on LAG-3.