Lumiliximab is a chimeric macaque-human
monoclonal antibody to CD23, a
protein expressed on virtually all
chronic lymphocytic leukemia (CLL) cells. We examined the ability of
lumiliximab to mediate apoptosis, antibody-dependent cellular cytotoxicity, and
complement-dependent cytotoxicity against primary CLL cells and CD23-expressing B-cell lines. Our data suggest that
lumiliximab kills CLL cells and CD23-expressing B cells predominantly by apoptosis, which occurs through the intrinsic pathway.
Lumiliximab-induced apoptosis was accompanied by the down-regulation of antiapoptotic
proteins Bcl-2, Bcl-X(L), and XIAP, activation of Bax, and release of
cytochrome c from the mitochondria. We also found that the addition of
lumiliximab to
rituximab or
fludarabine results in synergistic cytotoxicity of primary CLL cells and CD23-expressing B-cell lines. We investigated the in vivo activity of
lumiliximab in a human disseminated CD23(+)
B-cell lymphoma SCID mouse model and found greater antitumor activity with it than with control antibody. We also found that
paralysis-free survival was greater with
lumiliximab plus
rituximab or
fludarabine than with any of those agents alone. These results suggest that
lumiliximab may be an effective treatment alone or in combination with
rituximab or
chemotherapy agents in CLL or other CD23-overexpressing B-cell
malignancies.