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

In 1997, a chimeric anti-CD20 monoclonal antibody (mAb) (Rituxan) was appro ved 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 stud ies with mAbs that react with neoplastic B cells have demonstrated that hom odimers of immunoglobulin G ([IgG](2)) often inhibit cell growth more effec tively than their monomeric (IgG)(1) counterparts. In this study, the abili ty 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 li nes in vitro. It was found that homodimers of Rituxan had superior antigrow th activity in vitro and that F(ab')2 homodimers were the most active. Homo dimers, 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 ce lls more sensitive to chemotherapeutic agents and synergized with an anti-C D22 immunotoxin in vitro. (Blood, 2001;97: 1392-1398) (C) 2001 by The Ameri can Society of Hematology.