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

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.

journal_name

Blood

journal_title

Blood

authors

Gopal AK,Press OW,Wilbur SM,Maloney DG,Pagel JM

doi

10.1182/blood-2008-01-132142

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

830-5

issue

3

eissn

0006-4971

issn

1528-0020

pii

blood-2008-01-132142

journal_volume

112

pub_type

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