Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas

Abstract

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]