Very interesting on invitro activity of BEX v Rit. Unlabeled Bex seems to be more active.
v1
[4745] COMPARATIVE IN VITRO ACTIVITY OF TWO ANTI-CD20 ANTIBODIES- TOSITUMOMAB AND RITUXIMAB.
Pina M. Cardarelli, Maire Quinn, Yu Fang, David Colcher, David King, Christopher Bebbington, Geoffrey Yarranton (Intr. by Kari C. Nadeau)
CD20 is a B cell specific cell surface protein expressed on mature B lymphocytes and is a target for monoclonal antibody therapy in non-Hodgkin lymphoma (NHL). Though clear in vivo efficacy has been demonstrated with several anti-CD20 antibodies, the mechanism of action remains unclear. Proposed mechanisms of action include antibody dependent cell mediated cytotoxicity (ADCC), complement dependent cytotoxicity (CDC) and induction of apoptosis. In this report we compared the activity of anti-CD20 antibodies in a variety of cellular assays using a panel of B-cell lines. Anti-B1 antibody (tositumomab) showed activity in a CDC assay against complement sensitive cell lines, Ramos and Daudi. Using Raji cells as target cells and human peripheral blood leukocytes as effector cells, tositumomab was also a potent inducer of ADCC. In addition, tositumomab showed direct induction of apoptosis in all B-cell lines tested including NHL derived cell line DHL-4 which overexpresses the apoptotic-regulatory protein, bcl-2. In general, crosslinking the antibody with a goat anti-mouse Ig did not enhance the percentage of cells undergoing apoptosis. A second anti-CD20 antibody, C2B8 (rituximab), which binds to an overlapping epitope on CD20 with a three fold lower affinity than tositumomab, induced apoptosis in the cell lines tested when it was crosslinked with goat anti-human Ig. Like tositumomab, rituximab induced complement dependent lysis in several cell lines, but with different potencies. The activities of tositumomab and rituximab were nearly identical in the ADCC assay. Thus these two anti-CD20 antibodies have overlapping but distinct mechanisms of action on B-cell lines. In summary, the data indicate that tositumomab directly induces apoptosis. The signaling pathways leading to these events require further studies. Tositumomab is currently under investigation as one component of Bexxar, a radioimmunotherapy for treatment of NHL. The data suggest enhanced activity of unlabeled tositumomab over rituximab in several in vitro assays.
Keywords: Rituximab; Monoclonal antibodies |
