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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1392-1398
NEOPLASIA
Homodimers but not monomers of Rituxan (chimeric anti-CD20)
induce apoptosis in human B-lymphoma cells and synergize with a
chemotherapeutic agent and an immunotoxin
Maria-Ana Ghetie,
Helen Bright, and
Ellen S. Vitetta
From the Cancer Immunobiology Center, University of
Texas Southwestern Medical Center at Dallas, TX.
In 1997, a chimeric anti-CD20 monoclonal antibody (mAb)
(Rituxan) was approved for the treatment of
low-grade/follicular B-cell lymphoma. Rituxan has a long half-life and
low immunogenicity, and it mediates effector function. Rituxan induces
apoptosis in some tumor cell lines in vitro. Previous studies with mAbs
that react with neoplastic B cells have demonstrated that homodimers of
immunoglobulin G ([IgG]2) often inhibit cell
growth more effectively than their monomeric (IgG)1
counterparts. In this study, the ability of IgG or
F(ab')2 homodimers vs monomers of Rituxan were
compared for their ability to inhibit the growth of several
different B-lymphoma cell lines in vitro. It was found that homodimers
of Rituxan had superior antigrowth activity in vitro and that
F(ab')2 homodimers were the most active.
Homodimers, but not monomers, of Rituxan induced both apoptosis
and necrosis of several B-cell lymphoma lines in vitro; the inhibition
of cell growth was not dependent upon the presence of Fc receptors
or upon 10-fold or greater differences in the density of CD20
on the target cells. Rituxan homodimers, compared with monomers, also
rendered drug-resistant CD20+ B-lymphoma cells more
sensitive to chemotherapeutic agents and synergized with an anti-CD22
immunotoxin in vitro.
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