| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 152, Issue 5 2385-2392, Copyright © 1994 by American Association of Immunologists
ARTICLES |
GJ Weiner, SA Kostelny, JR Hillstrom, MS Cole, BK Link, SL Wang and JY Tso
University of Iowa Department of Internal Medicine, Iowa City 52242.
Anti-CD3 x antitumor bispecific Ab can retarget T cell mediated lysis in an MHC-independent fashion and prevent tumor growth in animal models. Two bispecific Ab preparations that differ in the presence or absence of Fc were compared in the 38C13 immunocompetent murine lymphoma model to evaluate how functional Fc and T cell activation impact on response to bispecific Ab therapy. Bispecific (bs) IgG contained functional Fc and was purified from hybrid-hybridoma Ab product. Bsf(ab')2 lacked functional Fc, and was genetically constructed using the leucine zipper technique. In vitro, bsF(ab')2 induced tumor cell lysis by activated T cells more effectively than bsIgG. However, bsF(ab')2 failed to induce T cell activation in the absence of tumor cells, and did so more slowly than bsIgG when tumor cells were present. In vivo, bsIgG induced nonspecific T cell activation whereas bsF(ab')2 did not. In therapy experiments, bsIgG inhibited tumor growth in mice although a single dose of bsF(ab')2 had minimal antitumor effect. BsF(ab')2 was capable of preventing tumor growth and improving survival when mice were also treated with T cell activators (IL-2 or staphylococcal enterotoxin B), or given repeated bsF(ab')2 doses. We conclude that therapeutic response to bispecific Ab was not dependent on functional Fc, but did require T cell activation. The use of bifunctional constructs that lack functional Fc therefore allows for separate manipulation of T cell retargeting and T cell activation and deserves further evaluation as a potential immunotherapy for malignancy.
This article has been cited by other articles:
|
|
 |
|
  S.-Y. Wang, E. Racila, R. P. Taylor, and G. J. Weiner NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement Blood, February 1, 2008; 111(3): 1456 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Shahied, Y. Tang, R. K. Alpaugh, R. Somer, D. Greenspon, and L. M. Weiner Bispecific Minibodies Targeting HER2/neu and CD16 Exhibit Improved Tumor Lysis When Placed in a Divalent Tumor Antigen Binding Format J. Biol. Chem., December 24, 2004; 279(52): 53907 - 53914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ruf and H. Lindhofer Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody Blood, October 15, 2001; 98(8): 2526 - 2534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. McCall, L. Shahied, A. R. Amoroso, E. M. Horak, H. H. Simmons, U. Nielson, G. P. Adams, R. Schier, J. D. Marks, and L. M. Weiner Increasing the Affinity for Tumor Antigen Enhances Bispecific Antibody Cytotoxicity J. Immunol., May 15, 2001; 166(10): 6112 - 6117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Warren, S. K. Bhatia, A. M. Acosta, C. E. Dahle, T. L. Ratliff, A. M. Krieg, and G. J. Weiner APC Stimulated by CpG Oligodeoxynucleotide Enhance Activation of MHC Class I-Restricted T Cells J. Immunol., December 1, 2000; 165(11): 6244 - 6251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Loffler, P. Kufer, R. Lutterbuse, F. Zettl, P. T. Daniel, J. M. Schwenkenbecher, G. Riethmuller, B. Dorken, and R. C. Bargou A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes Blood, March 15, 2000; 95(6): 2098 - 2103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Wild, W. Strittmatter, S. Matzku, B. Schraven, and S. C. Meuer Tumor Therapy with Bispecific Antibody: The Targeting and Triggering Steps Can Be Separated Employing a CD2-Based Strategy J. Immunol., August 15, 1999; 163(4): 2064 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zeidler, G. Reisbach, B. Wollenberg, S. Lang, S. Chaubal, B. Schmitt, and H. Lindhofer Simultaneous Activation of T Cells and Accessory Cells by a New Class of Intact Bispecific Antibody Results in Efficient Tumor Cell Killing J. Immunol., August 1, 1999; 163(3): 1246 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Strau{beta}, B. Guckel, D. Wallwiener, and G. Moldenhauer Without Prior Stimulation, Tumor-associated Lymphocytes from Malignant Effusions Lyse Autologous Tumor Cells in the Presence of Bispecific Antibody HEA125xOKT3 Clin. Cancer Res., January 1, 1999; 5(1): 171 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. De Jonge, C. Heirman, M. d. Veerman, S. Van Meirvenne, M. Moser, O. Leo, and K. Thielemans In Vivo Retargeting of T Cell Effector Function by Recombinant Bispecific Single Chain Fv (Anti-CD3 Anti-Idiotype) Induces Long-Term Survival in the Murine BCL1 Lymphoma Model J. Immunol., August 1, 1998; 161(3): 1454 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Chau, J. A. Bluestone, and J. Madrenas Dissociation of Intracellular Signaling Pathways in Response to Partial Agonist Ligands of the T Cell Receptor J. Exp. Med., May 18, 1998; 187(10): 1699 - 1709. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
