Apoptosis inducing bivalent single-chain antibody fragments against CD47 showed antitumor potency for multiple myeloma

被引：59

作者：

Kikuchi, Y ^{[1
]}

Uno, S ^{[1
]}

Kinoshita, Y ^{[1
]}

Yoshimura, Y ^{[1
]}

Iida, S ^{[1
]}

Wakahara, Y ^{[1
]}

Tsuchiya, M ^{[1
]}

Yamada-Okabe, H ^{[1
]}

Fukushima, N ^{[1
]}

机构：

[1] Chugai Pharmaceut Co Ltd, Fuji Gotemba Res Labs, Shizuoka 4128513, Japan

来源：

LEUKEMIA RESEARCH | 2005年 / 29卷 / 04期

关键词：

agonist antibody; scFv; diabody; CD47; apoptosis; myeloma;

D O I：

10.1016/j.leukres.2004.09.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Multiple myeloma is currently considered incurable despite the use of high-dose chemotherapy with autologous hematopoiefic 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. (c) 2004 Elsevier Ltd. All rights reserved.

引用

页码：445 / 450

页数：6

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