Combination with a Defucosylated Anti-HM1.24 Monoclonal Antibody Plus Lenalidomide Induces Marked ADCC Against Myeloma Cells and Their Progenitors

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jan 4

PMID 24386306

Citations 9

Authors

Takeshi Harada

Shuji Ozaki

Asuka Oda

Daisuke Tsuji

Akishige Ikegame

Masami Iwasa

Kengo Udaka

Shiro Fujii

Shingen Nakamura

Hirokazu Miki

Kumiko Kagawa

Yoshiaki Kuroda

Shigeto Kawai

Kohji Itoh

Hisafumi Yamada-Okabe

Toshio Matsumoto

Masahiro Abe

Affiliations

Soon will be listed here.

Abstract

The immunomodulatory drug lenalidomide (Len) has drawn attention to potentiate antibody-dependent cellular cytotoxicity (ADCC)-mediated immunotherapies. We developed the defucosylated version (YB-AHM) of humanized monoclonal antibody against HM1.24 (CD317) overexpressed in multiple myeloma (MM) cells. In this study, we evaluated ADCC by YB-AHM and Len in combination against MM cells and their progenitors. YB-AHM was able to selectively kill via ADCC MM cells in bone marrow samples from patients with MM with low effector/target ratios, which was further enhanced by treatment with Len. Interestingly, Len also up-regulated HM1.24 expression on MM cells in an effector-dependent manner. HM1.24 was found to be highly expressed in a drug-resistant clonogenic "side population" in MM cells; and this combinatory treatment successfully reduced SP fractions in RPMI 8226 and KMS-11 cells in the presence of effector cells, and suppressed a clonogenic potential of MM cells in colony-forming assays. Collectively, the present study suggests that YB-AHM and Len in combination may become an effective therapeutic strategy in MM, warranting further study to target drug-resistant MM clonogenic cells.

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