title: Apoptosis inducing bivalent single-chain antibody fragments against CD47 showed antitumor potency for multiple myeloma.
abstract: Multiple myeloma is currently considered incurable despite the use of high-dose chemotherapy with autologous hematopoietic stem cell transplantation support. Here, we show antitumor efficacy of a novel bivalent single-chain antibody fragment (scFv) against CD47 in an in vivo myeloma model. We generated two types of novel scFv molecules against CD47 having apoptosis-inducing activity for leukemic cell lines: a non-covalently linked scFv dimer (diabody) and a covalently linked bivalent scFv. Administration of these bivalent scFvs significantly prolonged the survival of mice transplanted with KPMM2 human myeloma cells. Because bivalent scFvs induced neither ADCC nor CDC, such antitumor activity by bivalent scFv is presumably attributable to cell death caused by the ligation of CD47. Thus, these apoptosis-inducing scFvs will be effective as a novel therapy for multiple myeloma which is considered incurable with conventional therapy.
authors.affiliation: Chugai Pharmaceutical Co. Ltd., Fuji-Gotemba Research Laboratories, 1-135 Komakado, Gotemba-shi, Shizuoka-ken 412-8513, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Uno
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Iida
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wakahara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yamada-Okabe
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D051928:CD47 Antigen; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology* / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000097:blood; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D051928:CD47 Antigen; C497894:CD47 protein, human; C497895:Cd47 protein, mouse; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G