PLoS ONE (Jan 2013)

Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0083905
Journal volume & issue
Vol. 8, no. 12
p. e83905

Abstract

Read online

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.