Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas.
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.
Israel
Bruce F
BF
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gulley
Margaret
M
Elmore
Sandra
S
Ferrini
Silvano
S
Feng
Wen-hai
WH
Kenney
Shannon C
SC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D053282:CD27 Ligand; D003165:Complement System Proteins / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D048069:Tumor Necrosis Factors / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; C505772:Cd70 protein, mouse; D008565:Membrane Proteins; D048069:Tumor Necrosis Factors; D003165:Complement System Proteins