A new target for enhancing tumor immunotherapy: ADORA2B (adenosine A2B receptor)

Introduction to Adenosine Receptors

Adenosine plays an important role in various physiological functions, and adenosine receptors (AR) have attracted attention as a potential drug therapy target. Adenosine receptors belong to the G protein-coupled receptor (GPCR) superfamily, including A1, A2A, A2B, and A3 subtypes. Among them, A2B receptors have a special low affinity for adenosine, and high concentrations of adenosine ( >25 uM), A2BR can activate cAMP and downstream pathways, and is related to immunosuppression, so it has application value in asthma and tumor immunotherapy.

Existing tumor immunotherapy has low efficacy and low or no response to many "cold" tumors. In response to this problem, studies have found that one of the main reasons for poor response is the existence of substances that suppress immune cells in the tumor microenvironment. Adenosine is one of the important substances that produce tumor immunosuppression in the tumor microenvironment, which inhibits the immune activity of immune cells by binding to A2A and A2B receptors. In this process, the proteins CD39-CD73-A2AR/A2BR are the most important, and the mechanism of action is as follows:

1. When there is tissue disorder (such as inflammation, malignant tumor, etc.) in the body, a large amount of intracellular ATP will be released outside the cell, and these ATP will be hydrolyzed by the extracellular nucleotide hydrolase CD39 into ADP and AMP;

2. The synergistic effect of AMP on CD73 dephosphorylates to generate immunosuppressive adenosine;

3. Adenosine binds to A2A and A2B receptors of immune cells around the tumor, activates cell signaling pathways, and leads to immunosuppression. In addition, studies have shown that the activation of tumor cell A2B receptors can also stimulate tumor cell metastasis and spread.

Research and Development Status of Adenosine A2B Receptor Drugs

At present, there are no adenosine A2B receptor drugs on the market, and the drugs under development are divided into two categories, one is selective adenosine A2B receptor small molecule antagonists, which can be divided into xanthines and Two kinds of non-xanthines, and the other is the antibody drug of A2B receptor, can be used as a combination and combined with immunotherapy drugs to enhance the efficacy and efficiency of immunotherapy.

A2B receptor target drug screening cell model

In response to the needs of A2B receptor mechanism research and new drug development, we have launched a series of A2B receptor drug screening cell models. Some data are shown below. Welcome to inquire.

Product List

Partial data display

1. hADORA2B/CHO RQP71368

Figure 3. NECA efffect on hA2B clone 11.

2. mADORA2B/CHO RQP71367

Fig 4. NECA efffect on CHO-K1-mA2B-clone 6.

3. Human ADORA2B Ga15/CHO RQP71019

Fig 5. Human ADORA2B Ga15/CHO ‍Representative Data.