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Apoptosis of Malignant Human B Cells by Ligation of CD20 With
Monoclonal Antibodies
Daming Shan,
Jeffrey A. Ledbetter, and
Oliver W. Press
From the Departments of Biological Structure and Medicine of the
University of Washington; the Fred Hutchinson Cancer Research Center;
and Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle,
WA.
CD20 is a nonglycosylated 33 to 37 kD phosphoprotein involved in
B-cell signaling that subserves important functions in the regulation
of B-cell proliferation and differentiation. In addition, this B-cell
surface antigen has been shown recently to be an effective target for
immunotherapy of B-cell malignancies using chimeric (mouse/human) or
radiolabeled murine monoclonal anti-CD20 antibodies. In this report we
show that extensive crosslinking of CD20 with murine anti-CD20
monoclonal antibodies (MoAbs) in the presence of either goat anti-mouse
IgG or Fc receptor (FcR)-expressing cells directly inhibits B-cell
proliferation, induces nuclear DNA fragmentation, and leads to cell
death by apoptosis. The apoptotic effects of these MoAbs can be
inhibited by chelation of extracellular or intracellular
Ca2+ by EGTA or Bapta AM, indicating that
anti-CD20-mediated apoptosis may be related to changes in
Ca2+ concentration. These findings suggest that ligation
of CD20 in vivo by anti-CD20 antibodies in the presence of
FcR-expressing cells may initiate signal transduction events that
induce elevation of [Ca2+]i and lead to
apoptosis of malignant B cells, thereby contributing to the impressive
tumor regressions observed in mouse models and clinical trials using
anti-CD20 MoAbs.
Blood, Vol. 91 No. 5 (March 1), 1998:
pp. 1644-1652
© 1998 by The American Society of Hematology.
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|
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|
|
|
|
|
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|
|
|
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|
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|
|
|
|
|
|
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J. M. Bennett, M. S. Kaminski, J. P. Leonard, J. M. Vose, A. D. Zelenetz, S. J. Knox, S. Horning, O. W. Press, J. A. Radford, S. M. Kroll, et al.
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|
|
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|
|
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[Full Text]
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|
|
|
|
|
|
|
L. A. Mosquera, K. F. Card, S. A. Price-Schiavi, H. J. Belmont, B. Liu, J. Builes, X. Zhu, P.-A. Chavaillaz, H.-i. Lee, J.-a. Jiao, et al.
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174(7):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hamaguchi, J. Uchida, D. W. Cain, G. M. Venturi, J. C. Poe, K. M. Haas, and T. F. Tedder
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April 1, 2005;
174(7):
4389 - 4399.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. N. Gordan, W. B. Grow, A. Pusateri, V. Douglas, N. P. Mendenhall, and J. W. Lynch
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February 20, 2005;
23(6):
1096 - 1102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Kaminski, M. Tuck, J. Estes, A. Kolstad, C. W. Ross, K. Zasadny, D. Regan, P. Kison, S. Fisher, S. Kroll, et al.
131I-Tositumomab Therapy as Initial Treatment for Follicular Lymphoma
N. Engl. J. Med.,
February 3, 2005;
352(5):
441 - 449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Horning, A. Younes, V. Jain, S. Kroll, J. Lucas, D. Podoloff, and M. Goris
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J. Clin. Oncol.,
February 1, 2005;
23(4):
712 - 719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F. DiJoseph, M. E. Goad, M. M. Dougher, E. R. Boghaert, A. Kunz, P. R. Hamann, and N. K. Damle
Potent and Specific Antitumor Efficacy of CMC-544, a CD22-Targeted Immunoconjugate of Calicheamicin, against Systemically Disseminated B-Cell Lymphoma
Clin. Cancer Res.,
December 15, 2004;
10(24):
8620 - 8629.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Roccatello, S. Baldovino, D. Rossi, M. Mansouri, C. Naretto, M. Gennaro, R. Cavallo, M. Alpa, P. Costanzo, O. Giachino, et al.
Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis
Nephrol. Dial. Transplant.,
December 1, 2004;
19(12):
3054 - 3061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Smith, F. Jin, and I. Joshi
Enhanced efficacy of therapy with antisense BCL-2 oligonucleotides plus anti-CD20 monoclonal antibody in scid mouse/human lymphoma xenografts
Mol. Cancer Ther.,
December 1, 2004;
3(12):
1693 - 1699.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Davis, M. S. Kaminski, J. P. Leonard, F. J. Hsu, M. Wilkinson, A. Zelenetz, R. L. Wahl, S. Kroll, M. Coleman, M. Goris, et al.
The Radioisotope Contributes Significantly to the Activity of Radioimmunotherapy
Clin. Cancer Res.,
December 1, 2004;
10(23):
7792 - 7798.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Stein, Z. Qu, T. M. Cardillo, S. Chen, A. Rosario, I. D. Horak, H. J. Hansen, and D. M. Goldenberg
Antiproliferative activity of a humanized anti-CD74 monoclonal antibody, hLL1, on B-cell malignancies
Blood,
December 1, 2004;
104(12):
3705 - 3711.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Cartron, H. Watier, J. Golay, and P. Solal-Celigny
From the bench to the bedside: ways to improve rituximab efficacy
Blood,
November 1, 2004;
104(9):
2635 - 2642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Eisenbeis, A. Grainger, B. Fischer, R. A. Baiocchi, L. Carrodeguas, S. Roychowdhury, L. Chen, A. L. Banks, T. Davis, D. Young, et al.
Combination Immunotherapy of B-Cell Non-Hodgkin's Lymphoma with Rituximab and Interleukin-2: A Preclinical and Phase I Study
Clin. Cancer Res.,
September 15, 2004;
10(18):
6101 - 6110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Leonard, M. Coleman, J. C. Ketas, A. Chadburn, R. Furman, M. W. Schuster, E. J. Feldman, M. Ashe, S. J. Schuster, W. A. Wegener, et al.
Epratuzumab, a Humanized Anti-CD22 Antibody, in Aggressive Non-Hodgkin's Lymphoma: Phase I/II Clinical Trial Results
Clin. Cancer Res.,
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