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 Blood, 1 August 2008, Vol. 112, No. 3, pp. 830-835.
Prepublished online as a Blood First Edition Paper on May 23, 2008; DOI 10.1182/blood-2008-01-132142.

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NEOPLASIA

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

Ajay K. Gopal1,2, Oliver W. Press1,2, Shani M. Wilbur2, David G. Maloney1,2, and John M. Pagel1,2

1 Department of Medicine, Division of Medical Oncology, University of Washington, Seattle; and 2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA

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) 131iodine-tositumomab and 90yttrium-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 µg/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 µg/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.


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