Since developed in 1980s by Prof. Richard Lerner and Prof. Gregory Winter, 2018 Nobel Laureate in Chemistry, combinatorial antibody library technology has been applied in biomedical development and basic science research, etc. Prof. Richard Lerner extended the application of combinatorial antibody to many fields, such as enzyme catalysis, receptor activation and cell fate regulators. Recently, a joint team led by Profs. Richard Lerner and Yang Guang discovered an agonist antibody targeting leptin receptor from combinatorial antibody and published their findings in Advanced Science on July 1st, entitled “Selection of a Full Agonist Combinatorial Antibody that Rescues Leptin Deficiency In Vivo”.
Leptin is an important protein metabolic regulator and it is mainly secreted by white adipose tissue of the body. Leptin can stimulate POMC and AgRP neurons, which express leptin receptor in the arcuate nucleus of the hypothalamus to regulate the body's appetite and energy metabolism. Leptin receptor belongs to the type I cytokine receptor family and the JAK-STAT pathway is its primary signaling.Leptin is a multi-function cytokine with many targeting organs. In addition to the regulation of energy metabolism, leptin also has many other important physiological functions, including immune regulation, reproductive system development, bone density regulation, nerve cell protection and tumorigenesis. Patients with leptin gene deficiency were clinically manifested as obesity, exuberant appetite, hyperinsulinemia, hyperlipidemia, and reproductive and immune dysfunction. The recombinant leptin has been approved in the United States, Europe and Japan for the treatment of patients with congenital or acquired systemic fat metabolism disorders that are complications of leptin deficiency. However, although recombinant leptin can effectively treat leptin deficiency in the body, the drug has a short half-life and immunogenicity, which may lead to the emergence of anti-drug antibodies and loss of therapeutic effect or severe infection.
https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202000818
