背景介绍 Adenosine signaling plays an important role in inflammation and the immune response. Many cells in the tumor microenvironment express ectopic CD39 and CD73, leading to the buildup of extracellular adenosine. Engagement of adenosine with the high affinity A2a receptor (A2aR) on the surface of T cells, macrophages, NK cells, neutrophils, and dendritic cells causes downregulation of the immune response. Therefore, A2aR is a novel immune checkpoint protein, and blockade of A2aR is being actively investigated as a potential immunotherapy.
Several A2aR antagonists have progressed to clinical trials for the treatment of Parkinson's disease, and preclinical studies have confirmed that blockade of A2a receptor activation has the ability to markedly enhance anti-tumor immunity. Mice treated with A2aR antagonists, such as ZM241385 (see data below) or caffeine, show significantly delayed tumor growth, and A2aR knockout mice demonstrate increased tumor rejection. Most promising, A2aR blockade can be used in synergy with the inhibition of other immune checkpoint pathways. Studies show that the combination of A2aR blockade and PD-1 inhibition is more effective than either treatment separately, and A2aR blockade increases the activity of CTLA-4 and TIM-3 inhibition in controlling the growth of CD73+ melanoma. 产品介绍 Adenosine A2a receptor (A2aR or ADORA2A) stably expressed in HEK-293 cells. A2aR is a member of the seven transmembrane G protein-coupled receptor (GPCR) family. The activity of A2aR is mediated by Gs protein which activates adenylyl cyclase, resulting in the synthesis of intracellular cAMP. The level of cAMP correlates with the respective adenosine (agonist) level, and the cell line can be used to measure the EC50 and IC50 values of A2aR agonists or antagonists in a quantitative manner. Binding of extracellular adenosine ligand or its stable analog NECA (5′-(N-Ethylcarboxamido) adenosine) to the A2aR expressed on the surface of this cell line induces cAMP expression.