Improving the treatment of non-Hodgkin lymphoma with antibody-targeted radionuclides

Authors

  • Robert M. Sharkey PhD,

    Corresponding author
    1. Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, New Jersey
    • Center for Molecular Medicine and Immunology, Garden State Cancer Center 520, Belleville Avenue, Belleville, NJ 07109
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    • Fax: (973) 844-7020

  • Habibe Karacay PhD,

    1. Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, New Jersey
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  • David M. Goldenberg ScD, MD

    1. Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, New Jersey
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  • The articles in this supplement were presented at the “12th Conference on Cancer Therapy with Antibodies and Immunoconjugates,” in Parsippany, New Jersey, October 16-18, 2008.

Abstract

Radioimmunotherapy of non-Hodgkin lymphoma comprises a 90Y- or 131I-labeled murine anti-CD20 IgG, but both agents also include a substantial dose of unlabeled anti-CD20 IgG given immediately before the radioconjugate to reduce its uptake in the spleen (primary normal B-cell antigen sink); this extends its plasma half-life and improves tumor visualization. Thus, these treatments combine an effective anti-CD20 radioconjugate with an unconjugated anti-CD20 antibody that is also therapeutically active, but the large anti-CD20 IgG predose (∼900 mg) may diminish the tumor localization of the radioimmunoconjugate (eg, 10-35 mg). We have examined alternative approaches that enhance radionuclide targeting and improve antitumor responses. One uses a 90Y-labeled anti-CD22 IgG (epratuzumab) combined with an antibody therapy regimen of a humanized anti-CD20 IgG (veltuzumab). Pretargeted radionuclide therapy using a trivalent, humanized, recombinant bispecific anti-CD20 antibody with a 90Y-hapten-peptide is another highly effective method that is also less toxic than directly radiolabeled IgG. Finally, all approaches benefit from the addition of a consolidation-dosing regimen of the anti-CD20 IgG antibody. This article reviews these various options and discusses how some fundamental changes could potentially enhance the response and duration from radionuclide-targeted therapy Cancer 2010;116(4 suppl):1134–45. © 2010 American Cancer Society.

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