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.

• Authors: Bruce F Israel, Margaret Gulley, Sandra Elmore, Silvano Ferrini, Wen-hai Feng, Shannon C Kenney
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 4 Issue 12 Pg. 2037-44 (Dec 2005) ISSN: 1535-7163 [Print] United States
• PMID: 16373719 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• CD27 Ligand
• CD70 protein, human
• Cd70 protein, mouse
• Membrane Proteins
• Tumor Necrosis Factors
• Complement System Proteins

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Antigens, CD (immunology)
• Apoptosis
• Burkitt Lymphoma (immunology, pathology, therapy, virology)
• CD27 Ligand
• Complement System Proteins (physiology)
• Herpesvirus 4, Human (isolation & purification)
• Humans
• Membrane Proteins (immunology)
• Mice
• Mice, SCID
• Tumor Necrosis Factors (immunology)