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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. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-132142v1 112/3/830    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gopal, A. K Articles by Pagel, J. M Search for Related Content PubMed PubMed Citation Articles by Gopal, A. K Articles by Pagel, J. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 3, 2008 Accepted April 30, 2008 Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45-Ab Ajay K Gopal*, Oliver W. Press, Shani M Wilbur, David G Maloney, and John M Pagel Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, United States Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States * Corresponding author; email: agopal{at}u.washington.edu. 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) 131I-Tositumomab and 90Y-Ibritumomab Tiuxetan. Hence, we assessed the impact of preexisting rituximab on the binding and efficacy of second anti-CD20 MoAbs to B-NHL and determined if this effect could be circumvented by targeting an alternative lymphoma-associated antigen, CD45. We demonstrated that rituximab concentrations as low as 5µg/ml nearly completely blocked the binding of a second anti-CD20 MoAbs (p=.00027), 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 7µg/ml, but did not impact CD45 ligation. A mouse xenograft model (Granta, FL-18, Ramos) showed that rituximab pre-treatment 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Green, J. M. Pagel, E. R. Nemecek, Y. Lin, A. Kenoyer, A. Pantelias, D. K. Hamlin, D. S. Wilbur, D. R. Fisher, J. G. Rajendran, et al. Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates Blood, August 6, 2009; 114(6): 1226 - 1235. [Abstract] [Full Text] [PDF] T. Illidge and Y. Du When is a predose a dose too much? Blood, June 4, 2009; 113(23): 6034 - 6035. [Full Text] [PDF] A. K. Gopal, J. M. Pagel, J. R. Fromm, S. Wilbur, and O. W. Press 131I anti-CD45 radioimmunotherapy effectively targets and treats T-cell non-Hodgkin lymphoma Blood, June 4, 2009; 113(23): 5905 - 5910. [Abstract] [Full Text] [PDF] J. M. Pagel, N. Orgun, D. K. Hamlin, D. S. Wilbur, T. A. Gooley, A. K. Gopal, S. I. Park, D. J. Green, Y. Lin, and O. W. Press A comparative analysis of conventional and pretargeted radioimmunotherapy of B-cell lymphomas by targeting CD20, CD22, and HLA-DR singly and in combinations Blood, May 14, 2009; 113(20): 4903 - 4913. [Abstract] [Full Text] [PDF] R. M. Sharkey, O. W. Press, and D. M. Goldenberg A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy Blood, April 23, 2009; 113(17): 3891 - 3895. [Abstract] [Full Text] [PDF] H. Hochster, E. Weller, R. D. Gascoyne, T. M. Habermann, L. I. Gordon, T. Ryan, L. Zhang, N. Colocci, S. Frankel, and S. J. Horning Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study J. Clin. Oncol., April 1, 2009; 27(10): 1607 - 1614. [Abstract] [Full Text] [PDF] R. M. Sharkey, H. Karacay, C. R. Johnson, S. Litwin, E. A. Rossi, W. J. McBride, C.-H. Chang, and D. M. Goldenberg Pretargeted Versus Directly Targeted Radioimmunotherapy Combined with Anti-CD20 Antibody Consolidation Therapy of Non-Hodgkin Lymphoma J. Nucl. Med., March 1, 2009; 50(3): 444 - 453. [Abstract] [Full Text] [PDF] E. L.J.M. Smits, Z. N. Berneman, and V. F.I. Van Tendeloo Immunotherapy of Acute Myeloid Leukemia: Current Approaches Oncologist, March 1, 2009; 14(3): 240 - 252. [Abstract] [Full Text] [PDF] T. M. Illidge, M. Bayne, N. S. Brown, S. Chilton, M. S. Cragg, M. J. Glennie, Y. Du, V. Lewington, J. Smart, J. Thom, et al. Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy Blood, February 12, 2009; 113(7): 1412 - 1421. [Abstract] [Full Text] [PDF] O. W. Press Evidence Mounts for the Efficacy of Radioimmunotherapy for B-Cell Lymphomas J. Clin. Oncol., November 10, 2008; 26(32): 5147 - 5150. [Full Text] [PDF]

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