title: Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist.
abstract: In general, traditional growth hormone receptor antagonist can be divided into two major classes: growth hormone (GH) analogues and anti-growth hormone receptor (GHR) antibodies. Herein, we tried to explore a new class of growth hormone receptor (GHR) antagonist that may have potential advantages over the traditional antagonists. For this, we developed a monoclonal anti-idiotypic antibody growth hormone, termed CG-86. A series of experiments were conducted to characterize and evaluate this antibody, and the results from a competitive receptor-binding assay, Enzyme Linked Immunosorbent Assays (ELISA) and epitope mapping demonstrate that CG-86 behaved as a typical Ab2β. Next, we examined its antagonistic activity using in vitro cell models, and the results showed that CG-86 could effectively inhibit growth hormone receptor-mediated signalling and effectively inhibit growth hormone-induced Ba/F3-GHR638 proliferation. In summary, these studies show that an anti-idiotypic antibody (CG-86) has promise as a novel growth hormone receptor antagonist. Furthermore, the current findings also suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors.
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, PR China. Electronic address: tougao@jlau.edu.cn.
authors.forename: Hainan
authors.initials: H
authors.lastname: Lan
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Institute of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Muhammad Akram
authors.initials: MA
authors.lastname: Khan
authors.affiliation: EAC Center of Drug Development, Endocrine Biological Drug Co. Ltd, Shanghai 201203, PR China. Electronic address: stevenEAC@hotmail.com.
authors.forename: Steven
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001667:Binding, Competitive; D016466:CHO Cells; D002460:Cell Line; D049109:Cell Proliferation; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D015870:Gene Expression; D013006:Growth Hormone / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D011986:Receptors, Somatotropin; D013006:Growth Hormone
keywords: Anti-idiotypic antibody; GHR antagonist; Growth hormone; Growth hormone receptor; Intracellular signalling