Rituximab-Mediated Cell Signaling and Chemo/Immuno-sensitization of Drug-Resistant B-NHL Is Independent of Its Fc Functions
Por:
Vega M.I., Huerta-Yepez S., Martinez-Paniagua M., Martinez-Miguel B., Hernandez-Pando R., González-Bonilla C.R., Chinn P., Hanna N., Hariharan K., Jazirehi A.R., Bonavida B.
Publicada:
1 nov 2009
Resumen:
Purpose: Rituximab [chimeric anti-CD20 monoclonal antibody], alone or combined with chemotherapy, is used in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab binds to CD20 and inhibits intracellular survival/growth pathways leading to chemo/immunosensitization of tumor cells in vitro. The contribution of rituximab Fc-FcR interaction in signaling is not known. This study examined the role of Fc-FcR interactions in rituximab-induced signaling using rituximab (Fab')2 fragments as well as rituximab devoid of the CH2 Fc-binding domain (CH2(-)). Experimental Design: Rituximab (CH2(-)) and rituximab (Fab')(2) were tested for their activity on B-NHL cell lines. Cell signaling and sensitization to chemotherapy and immunotherapy were examined. The in vitro studies were validated in mice bearing tumor xenografts. Results: Although the modified antibodies were defective in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity functions, they retained all other biol
Filiaciones:
Vega M.I.:
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología, CMN La Raza, México City, Mexico
Huerta-Yepez S.:
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología, CMN La Raza, México City, Mexico
Martinez-Paniagua M.:
Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología, CMN La Raza, México City, Mexico
Martinez-Miguel B.:
Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología, CMN La Raza, México City, Mexico
Hernandez-Pando R.:
Sección de Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
González-Bonilla C.R.:
Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología, CMN La Raza, México City, Mexico
Chinn P.:
Biogen-Idec, Inc., San Diego, CA, United States
Hanna N.:
Biogen-Idec, Inc., San Diego, CA, United States
Hariharan K.:
Biogen-Idec, Inc., San Diego, CA, United States
Jazirehi A.R.:
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
Bonavida B.:
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
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