Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab.

Publication Type:

Journal Article

Source:

Blood, Volume 112, Issue 3, p.830-5 (2008)

Keywords:

2008, Animals, Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Antibody Development Core Facility, Antigens, CD20, Antigens, CD45, Antineoplastic Combined Chemotherapy Protocols, Biologics Production Core Facility, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, Drug Interactions, Female, Flow Cytometry Core Facility, Humans, Immunoconjugates, Iodine Radioisotopes, Lymphoma, B-Cell, MICE, Mice, Nude, Radioimmunotherapy, Shared Resources, Xenograft Model Antitumor Assays, Yttrium Radioisotopes

Abstract:

Rituximab therapy is associated with a long in vivo persistence, yet little is known about the effect of circulating rituximab on B-cell non-Hodgkin lymphoma (B-NHL) targeting by the other available anti-CD20 monoclonal antibodies (MoAbs) (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan. Therefore we assessed the impact of preexisting rituximab on the binding and efficacy of second anti-CD20 MoAbs to B-NHL and determined whether targeting an alternative lymphoma-associated antigen, CD45, could circumvent this effect. We demonstrated that rituximab concentrations as low as 5 microg/mL nearly completely blocked the binding of a second anti-CD20 MoAbs (P < .001), but had no impact on CD45 targeting (P = .89). Serum from patients with distant exposures to rituximab also blocked binding of anti-CD20 MoAbs to patient-derived rituximab-naive B-NHL at concentrations at low as 7 microg/mL, but did not affect CD45 ligation. A mouse xenograft model (Granta, FL-18, Ramos cell lines) showed that rituximab pretreatment significantly reduced B-NHL targeting and tumor control by CD20-directed radioimmunotherapy (RIT), but had no impact on targeting CD45. These findings suggest that circulating rituximab impairs the clinical efficacy of CD20-directed RIT, imply that novel anti-CD20 MoAbs could also face this same limitation, and indicate that CD45 may represent an alternative target for RIT in B-NHL.