Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies

作者: Daming Shan , Jeffrey A. Ledbetter , Oliver W. Press

DOI: 10.1182/BLOOD.V91.5.1644

关键词: MonoclonalImmunologyProgrammed cell deathAntibodyMolecular biologySignal transductionBiologyFc receptorApoptosisAntigenMonoclonal antibody

摘要: CD20 is a nonglycosylated 33 to 37 kD phosphoprotein involved in B-cell signaling that subserves important functions the regulation of proliferation and differentiation. In addition, this surface antigen has been shown recently be an effective target for immunotherapy malignancies using chimeric (mouse/human) or radiolabeled murine monoclonal anti-CD20 antibodies. report we show extensive crosslinking with antibodies (MoAbs) presence either goat anti-mouse IgG Fc receptor (FcR)-expressing cells directly inhibits proliferation, induces nuclear DNA fragmentation, leads cell death by apoptosis. The apoptotic effects these MoAbs can inhibited chelation extracellular intracellular Ca2+ EGTA Bapta AM, indicating anti-CD20–mediated apoptosis may related changes concentration. These findings suggest ligation vivo FcR-expressing initiate signal transduction events induce elevation [Ca2+]i lead malignant B cells, thereby contributing impressive tumor regressions observed mouse models clinical trials MoAbs.

参考文章(52)
Thomas F. Tedder, Arne Forsgren, Andrew W. Boyd, Lee M. Nadler, Stuart F. Schlossman, Antibodies reactive with the B1 molecule inhibit cell cycle progression but not activation of human B lymphocytes. European Journal of Immunology. ,vol. 16, pp. 881- 887 ,(1986) , 10.1002/EJI.1830160802
A. Constantinou, E. Huberman, Genistein as an Inducer of Tumor Cell Differentiation: Possible Mechanisms of Action Experimental Biology and Medicine. ,vol. 208, pp. 109- 115 ,(1995) , 10.3181/00379727-208-43841
Kirk Trisler, Tina Marie Liles, Ronald Levy, Susan J. Knox, Paul Chinn, Robert Negrin, Michael L. Goris, Sherry Fowler, Mark Becker, Antonio Grillo-López, Chet Varns, Carol Marquez, Thomas Davis, Nimisha Deb, Shou Cheng Ning, Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma Clinical Cancer Research. ,vol. 2, pp. 457- 470 ,(1996)
Mary A. Valentine, Karen A. Licciardi, Rescue from anti-IgM-induced programmed cell death by the B cell surface proteins CD20 and CD40 European Journal of Immunology. ,vol. 22, pp. 3141- 3148 ,(1992) , 10.1002/EJI.1830221217
Bayard D. Clarkson, Amaury G. Perez, Jerrold Fried, Properties of the Method and Mathematical Analysis of the Data ,(1976)
R. Marches, Ellen S Vitetta, L. Picker, R. Hsueh, E. Racila, J. W. Uhr, T. F. Tucker, R. H. Scheuermann, P. Mongini, Tumour dormancy and cell signalling - III: Role of hypercrosslinking of IgM and CD40 on the induction of cell cycle arrest and apoptosis in B lymphoma cells Therapeutic Immunology. ,vol. 2, pp. 125- 136 ,(1995)
Oliver W. Press, Janet F. Eary, Frederick R. Appelbaum, Paul J. Martin, Christopher C. Badger, Wil B. Nelp, Stephan Glenn, Greg Butchko, Darrell Fisher, Bruce Porter, Dana C. Matthews, Lloyd D. Fisher, Irwin D. Bernstein, Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support The New England Journal of Medicine. ,vol. 329, pp. 1219- 1224 ,(1993) , 10.1056/NEJM199310213291702
Kevin G. Waddick, HeonJoo Park Chae, Lisa Tuel-Ahlgren, Lisa J. Jarvis, Ilker Dibirdik, Dorothea E. Myers, Fatih M. Uckun, Engagement of the CD19 receptor on human B-lineage leukemia cells activates LCK tyrosine kinase and facilitates radiation-induced apoptosis. Radiation Research. ,vol. 136, pp. 313- 319 ,(1993) , 10.2307/3578542
OW Press, J Howell-Clark, S Anderson, I Bernstein, Retention of B-cell-specific monoclonal antibodies by human lymphoma cells Blood. ,vol. 83, pp. 1390- 1397 ,(1994) , 10.1182/BLOOD.V83.5.1390.1390
P. Sarthou, L. Benhamou, P.-A. Cazenave, B Cell Activation and Apoptosis Current Topics in Microbiology and Immunology. ,vol. 200, pp. 15- 37 ,(1995) , 10.1007/978-3-642-79437-7_2