Multiple Signaling Pathways Induced by Hexavalent, Monospecific and Bispecific Antibodies for Enhanced Toxicity to B-Cell Lymphomas and Other Diseases

作者: Chien-Hsing Chang , Edmund A. Rossi , David M. Goldenberg

DOI:

关键词:

摘要: Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, antibody is veltuzumab epratuzumab. Administration subject induces apoptosis cell death target cells in diseases such as B-cell lymphomas leukemias, autoimmune disease immune dysfunction disease. In most preferred embodiments, increase levels phosphorylated p38 PTEN, decrease Lyn, Akt, ERK, IKKα/β IκBα, expression RKIP Bax Mcl-1, Bcl-xL, Bcl-2, phospho-BAD cells. The show EC50 values for inhibiting tumor growth low nanomolar even sub-nanomolar concentration range.

参考文章(361)
Michael G. Baines, Robin Thorpe, Purification of Immunoglobulin G (IgG) Methods of Molecular Biology. ,vol. 10, pp. 79- 104 ,(1992) , 10.1385/0-89603-204-3:79
OW Press, F Appelbaum, JA Ledbetter, PJ Martin, J Zarling, P Kidd, ED Thomas, Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas Blood. ,vol. 69, pp. 584- 591 ,(1987) , 10.1182/BLOOD.V69.2.584.584
Klibanov Al, Torchilin Vp, The antibody-linked chelating polymers for nuclear therapy and diagnostics. Critical Reviews in Therapeutic Drug Carrier Systems. ,vol. 7, pp. 275- 308 ,(1991)
Arnold S. Freedman, Immunobiology of Chronic Lymphocytic Leukemia Hematology/Oncology Clinics of North America. ,vol. 4, pp. 405- 429 ,(1990) , 10.1016/S0889-8588(18)30495-7
Patricia A. Jennings, Marceen Glavic Newlon, Melinda Roy, Dimitrios Morikis, Zachary E. Hausken, Vincent Coghlan, John D. Scott, The molecular basis for protein kinase A anchoring revealed by solution NMR. Nature Structural & Molecular Biology. ,vol. 6, pp. 222- 227 ,(1998) , 10.1038/6663
Robert Eisenberg, R. John Looney, The therapeutic potential of anti-CD20: “What do B-cells do?” Clinical Immunology. ,vol. 117, pp. 207- 213 ,(2005) , 10.1016/J.CLIM.2005.08.006
Philip M. Grimley, Hui Fang, Hallgeir Rui, Emanuel F. Petricoin III, Subhransu Ray, Fan Dong, Karen H. Fields, Renqiu Hu, Kathryn C. Zoon, Susette Audet, Judy Beeler, Prolonged STAT1 Activation Related to the Growth Arrest of Malignant Lymphoma Cells by Interferon-α Blood. ,vol. 91, pp. 3017- 3027 ,(1998) , 10.1182/BLOOD.V91.8.3017.3017_3017_3027
Randy R. Robinson, John Chartier, C. Paul Chang, Arnold H. Horwitz, Marc Better, Chimeric mouse-human anti-carcinoma antibodies that mediate different anti-tumor cell biological activities Human antibodies. ,vol. 2, pp. 84- 93 ,(1991) , 10.3233/HAB-1991-2206