title: Establishment of a novel monoclonal antibody against LGR5.
abstract: LGR5 is an orphan G-protein-coupled receptor (GPCR) that is expressed on the cell surface membrane. LGR5 is reported to be overexpressed in colon, liver, and ovary tumor compared to normal tissue. However, a specific ligand for LGR5 has not yet been determined, and the function is still not clear. An LGR5-specific monoclonal antibody (mAb) is needed as a tool for detection and analysis of LGR5 biological function and cancer therapy. To date, no mAb against LGR5 that retains high affinity and specificity has been reported. Here, we report successful establishment and characterization of a mAb (KM4056) that specifically recognizes the extracellular N-terminal domain of human LGR5, but not LGR4 or LGR6. This mAb has potent complement-dependent cytotoxicity (CDC) activity in vitro and shows strong anti-tumor activity in vivo against xenograft model by transplanting LGR5 expressing CHO transfectants into SCID mice. Thus, KM4056 can be a useful tool for detection of LGR5 positive cells and analysis of LGR5 biological function.
authors.affiliation: Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kosaka
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Usami
authors.forename: Hiroe
authors.initials: H
authors.lastname: Toki
authors.forename: Hironori
authors.initials: H
authors.lastname: Kawai
authors.forename: Norihiko
authors.initials: N
authors.lastname: Shiraishi
authors.forename: Toshio
authors.initials: T
authors.lastname: Ota
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Nakamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Furuya
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Satoh
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Masuda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled