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¹ University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and ² Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Requests for reprints: Shannon C. Kenney, Lineberger Cancer Center, University of North Carolina at Chapel Hill, CB 7295, Chapel Hill, NC 27599-7295; Phone: 919-966-1248; Fax: 919-966-8212. E-mail: shann{at}med.unc.edu

A monoclonal antibody (Rituximab) directed against the B-cell surface antigen, CD20, is increasingly used as a therapy for B-cell lymphomas. However, CD20 is expressed on all normal mature B cells and hence is not a specific tumor target. In contrast, CD70 is expressed on highly activated lymphocytes as well as on many B-cell and T-cell lymphomas but is not expressed on the great majority of B cells and T cells. In this report, we have explored the potential utility of anti-CD70 monoclonal antibodies for treatment of CD70⁺ EBV⁺ B-cell lymphomas. Using two Burkitt's lymphoma lines (Raji and Jijoye) that express surface CD70 and a CD70^– Burkitt's lymphoma line (Akata), we show that two different monoclonal antibodies directed against human CD70 allow rabbit and human complement to kill EBV⁺ B cells in a CD70-dependent manner in vitro. In the absence of complement, neither anti-CD70 antibody induced in vitro killing of CD70⁺ cell lines. Importantly, i.p. injection of anti-CD70 antibodies also inhibited the growth of CD70⁺ Burkitt's lymphoma cells in severe combined immunodeficient mice but did not inhibit the growth of CD70^– Burkitt's lymphoma cells. These results suggest that anti-CD70 antibodies may be useful for the treatment of CD70⁺ B-cell lymphomas. [Mol Cancer Ther 2005;4(12):2037–44]

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Received 7/18/05; revised 9/ 7/05; accepted 9/21/05.