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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3922-3930
Humanized Anti-HM1.24 Antibody Mediates Myeloma Cell Cytotoxicity
That Is Enhanced by Cytokine Stimulation of Effector Cells
Shuji Ozaki,
Masaaki Kosaka,
Yuji Wakahara,
Yasuko Ozaki,
Masayuki Tsuchiya,
Yasuo Koishihara,
Tetsuya Goto, and
Toshio Matsumoto
From the First Department of Internal Medicine, School of Medicine,
University of Tokushima, Tokushima, and Fuji-Gotemba Research
Laboratory, Chugai Pharmaceutical Co, Ltd, Shizuoka, Japan.
To develop a new immunotherapy for multiple myeloma, we have
generated a monoclonal antibody (MoAb) that detects a human plasma cell-specific antigen, HM1.24. Our previous study has shown that mouse
anti-HM1.24 MoAb inhibits the proliferation of human myeloma cells
implanted into severe combined immunodeficiency mice. In this report,
we evaluated the antitumor activity of the humanized anti-HM1.24 MoAb
(IgG1 ), which was constructed by grafting the complementarity-determining regions. In contrast to the parent mouse
MoAb, humanized anti-HM1.24 MoAb mediated antibody-dependent cellular
cytotoxicity (ADCC) against both myeloma cell lines and myeloma cells
from patients in the presence of human peripheral blood mononuclear
cells (PBMCs). The PBMCs from untreated myeloma patients exhibited ADCC
activity as efficiently as those of healthy donors. Although decreased
ADCC activity of PBMCs was observed in patients who responded poorly to
conventional chemotherapy, it could be significantly augmented by the
stimulation with interleukin-2 (IL-2), IL-12, or IL-15. There was a
strong correlation between the percentage of CD16+ cells
and ADCC activity in the PBMCs of myeloma patients. Moreover, peripheral blood stem cell collections from myeloma patients contained higher numbers of CD16+ cells than PBMCs and exhibited
ADCC activity that was enhanced by IL-2. These results indicate that
humanized anti-HM1.24 MoAb has potential as a new therapeutic strategy
in multiple myeloma and that treatment of effector cells with
immunomodulating cytokines can restore the effect of humanized
anti-HM1.24 MoAb in patients with diminished ADCC activity.
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