Acquired immunodeficiency syndrome-associated lymphomas are efficiently lysed through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by rituximab.
Rituximab (Mabthera) and alemtuzumab (Campath(R), Mabcampath(R)) are non-conjugated IgG1 therapeutic monoclonal antibodies directed against the CD20 and CD52 surface antigens respectively. They are presently used in the therapy of indolent B-cell non-Hodgkin's lymphoma (B-NHL) and of B-cell chronic lymphocytic leukaemia, and are thought to act mainly through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Here we have analysed the capacity of these two monoclonal antibodies to lyse cell lines of acquired immunodeficiency syndrome (AIDS)-related B-NHL through either complement activation or antibody-dependent cytotoxicity. Rituximab strongly activated both CDC and ADCC against CD20-positive AIDS-NHL cells lines, inducing up to 60-98% and 20% specific lysis respectively. In contrast, alemtuzumab was a poor activator of CDC, even in the AIDS-NHL cell lines expressing high amounts of CD52, leading to a lysis of only 1-30%, whereas it was at least as strong as rituximab in inducing ADCC of the same lines (up to 30% specific lysis). Altogether, these data offer a first in vitro rationale supporting the therapeutic use of rituximab for CD20-positive AIDS-NHL.
Golay
Joseè
J
Laboratory of Molecular Immunohaematology, Department of Immunology and Cell Biology, Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
Gramigna
Rosanna
R
Facchinetti
Valeria
V
Capello
Daniela
D
Gaidano
Gianluca
G
Introna
Martino
M
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000276:immunology*; D016923:Cell Death; D003167:Complement Activation; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000473:pathology; D000069283:Rituximab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D000069283:Rituximab