Introduction to Agonistic and Antagonistic Antibody Discovery by Phage Display

Among the different branches of targeted drugs, monoclonal antibody drugs have gradually become the brightest pearl by virtue of their high specificity, high targeting, and other advantages. It plays an important role in fields such as oncology and autoimmune diseases and is even becoming a major direction of development in the field of biopharmaceuticals. And agonists or antagonists based on disease targets are one of the most effective ways to target immune responses and malignant tumors. Based on our rich field experience and phage display platform, Creative Biolabs provides comprehensive services to support custom agonistic antibodies and custom antagonistic antibodies.

Antibodies. (Creative Biolabs Authorized) Fig 1. Antibodies.

Agonistic & Antagonistic Antibodies

The immune checkpoint is an immune system regulator. It is essential for maintaining autoimmune tolerance and regulating the duration and scope of immune responses in peripheral tissues. However, these pathways can be "hijacked" and persistently activated by tumors, suppressing anti-tumor immunity and promoting tumorigenesis. There are two types of checkpoint molecules associated with immune regulation, agonistic and antagonistic checkpoint molecules.

Immunotherapy with immune checkpoint antagonists has led to leaps and bounds in the treatment of various types of cancer over the past decade. For more than a century, immune-based therapies have had small successes, with the identification and development of immune checkpoint-specific antagonists playing a key role. Among them, the research and application of PD-1/PD-L1 is the most mature, and it once became the "miracle drug against cancer" in the eyes of many people. PD-1 antagonists have many advantages. For example, PD-1 antagonistic treatment is not based on the source of the tumor but on biomarkers, and the anti-cancer effect is more broad-spectrum. PD-1 antagonists, if effective, may allow patients with advanced tumors to survive for a long time or even reach a clinical cure and are not easy to produce drug resistance. This is the biggest difference from other tumor treatment methods. In addition, different from traditional radiotherapy that "kills a thousand enemies and damages eight hundred", the principle of immunotherapy is not to enhance the killing power, but to activate one's own immune system to attack the tumor, so the overall side effects are much smaller.

With the discovery of immune checkpoint antagonists, scientists are gradually turning their attention to immune checkpoint agonists. Studies have shown that immune checkpoint agonists are also important in the treatment of immune disorders and other diseases. Especially in the field of oncology therapy, strategies to enhance anti-tumor immune response are one of the most promising new developments in oncology. And TNF-R-SF members, such as CD40, are among the important targets. Due to the unique requirements for generating efficient TNF-R-SF signaling, agonist molecules must produce very precise receptor structures and three-dimensional structures. Although various strategies for inducing CD40 signaling have been explored, 20 years of limited clinical success suggests that new approaches need to be explored and that the true power of agonists of this signaling pathway has not yet been fully unleashed in clinical development. However, there are reasons to believe that agonistic antibody has more surprises waiting for us to discover and study.

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Creative Biolabs has a wealth of knowledge and experience in phage display. We would be happy to share with you our knowledge and experience in agonistic and antagonistic antibody discovery by phage display.

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