Agonistic antibodies against immune co-stimulatory receptors have been tested in cancer clinics for more than 10 years. Creative Biolabs has more than 10 years of experience in producing highly specific and efficient antibodies. In the production of agonistic antibodies, we have provided high-quality one-stop services to customers from academic institutions and pharmaceutical companies.
Agonistic antibodies are antibodies designed to boost the immune system against infection or cancer. The desired and defining feature of agonistic antibodies is that they can bind and activate target receptors in a manner that mimics the activity of natural ligands. The role of antibodies as agonists may be influenced by a variety of factors, including binding epitopes, affinity, valence, receptor occupancy, and interaction between antibody crystallizable segment (Fc) domain and Fcγ receptors (FcγRs). Unlike antagonists, there is no hard rule to easily predict the potential of an antibody to act as an agonist.
Therefore, the process of identifying and developing agonistic antibodies is largely an empirical exercise driven by the characterization of antibody functions using cell-based and in vivo model systems. As a service provider with rich experience in the field of antibody production, Creative Biolabs has experts who have a detailed understanding of the specific chemometrics and binding properties of natural ligand-receptor complexes, which helps to design antibodies that have the best agonist function for specific receptors.
At present, Creative Biolab's development of agonistic antibodies mainly includes two major directions, namely, checkpoints and autoantibodies.
The function of immune cells is regulated by co-inhibitory and co-stimulatory receptors. In order to control the immune response and avoid chronic inflammation and autoimmunity, a variety of immune signaling pathways are used to stimulate or suppress the immune response in order to maintain internal balance. These signaling pathways are designed to allow the optimal immune response to foreign antigens but to prevent self-mutilation due to overreaction. These signals that regulate the immune response are called immune checkpoints. Compounds as immune checkpoints agonists must not only bind to receptors but also transmit signals through receptors. The challenges of checkpoint agonistic antibody development make it unique compared with other cancer antibody therapies. Looking forward to the future, there will be great prospects in targeting co-stimulatory receptors with agonistic antibodies. Of course, this is also a subject that we are constantly striving to improve in the field of antibody development.
Fig.1 Possible mechanisms of action of agonist agents, based on the kinetic-segregation model of receptor signaling. (Paluch, 2018)
Autoantibody is an antibody (a protein) produced by the immune system, which targets one or more proteins of an individual. Many autoimmune diseases are caused by stimulating autoantibodies against G protein-coupled receptors (GPCRs). These include stimulating antibodies against β1- and β2-adrenergic receptors (AR), α1-adrenergic receptors and angiotensin II AT1 receptors. Their existence and mode of action have been established. At present, the mechanism of receptor activation and transformation is being studied. The results show that receptor agonistic autoantibody is a valuable therapeutic target in the treatment of autoimmune diseases.
Fig.2 Pathological effects of anti-GPCRs autoantibodies interfering with neuronal transmission. (Cabral-Marques, 2017)
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