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Updated: Aug 12, 2026

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
Apoptosis inducing bivalent single-chain antibody fragments against CD47 showed antitumor potency for multiple
Yasufumi Kikuchi1, Shinsuke Uno, Yasuko Kinoshita
1Chugai Pharmaceutical Co. Ltd., Fuji-Gotemba Research Laboratories, 1-135 Komakado, Gotemba-shi, Shizuoka-ken 412-8513, Japan.
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.
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