|
|
Blood, 1 November 2005, Vol. 106, No. 9, pp. 3127-3133.
Prepublished online as a Blood First Edition Paper on July 21, 2005; DOI 10.1182/blood-2005-06-2298.
 Previous Article | Next Article 
Submitted June 8, 2005
Accepted June 30, 2005
Human CTLA-4-knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies
Kenneth D Lute, Kenneth F May, Ping Lu, Huiming Zhang, Ergun Kocak, Bedrick Mosinger, Christopher Wolford, Gary Phillips, Michael A Caligiuri, Pan Zheng, and Yang Liu*
Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio, USA
Neurobiotechnology Center, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio, USA
Center for Biostatistics, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio, USA
Department of Internal Medicine, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio, USA
* Corresponding author; email: liu-3{at}medctr.osu.edu.
Although results from preclinical studies in animal models have proven the concept for use of anti-CTLA-4 antibodies in cancer immunotherapy, two major obstacles have hindered their successful application for human cancer therapy. First, the lack of in vitro correlates of the anti-tumor effect of the antibodies makes it difficult to screen for the most efficacious antibody by in vitro analysis. Second, significant autoimmune side-effects have been observed in a recent clinical trial. In order to address these two issues, we have generated human CTLA-4 gene knock-in mice and used them to compare a panel of anti-human CTLA-4 antibodies for their ability to induce tumor rejection and autoimmunity. Surprisingly, while all antibodies induced protection against cancer and demonstrated some autoimmune side effects, the antibody that induced the strongest protection also induced the least autoimmune side effects. These results demonstrate that autoimmune disease does not quantitatively correlate with cancer immunity. Our approach may be generally applicable to the development of human therapeutic antibodies.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. S. Peggs, S. A. Quezada, C. A. Chambers, A. J. Korman, and J. P. Allison
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies
J. Exp. Med.,
August 3, 2009;
206(8):
1717 - 1725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Fadel, K. E. Karoui, and B. Knebelmann
Anti-CTLA4 Antibody-Induced Lupus Nephritis
N. Engl. J. Med.,
July 9, 2009;
361(2):
211 - 212.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gattinoni, A. Ranganathan, D. R. Surman, D. C. Palmer, P. A. Antony, M. R. Theoret, D. M. Heimann, S. A. Rosenberg, and N. P. Restifo
CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent
Blood,
December 1, 2006;
108(12):
3818 - 3823.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Kocak, K. Lute, X. Chang, K. F. May Jr., K. R. Exten, H. Zhang, S. F. Abdessalam, A. M. Lehman, D. Jarjoura, P. Zheng, et al.
Combination Therapy with Anti-CTL Antigen-4 and Anti-4-1BB Antibodies Enhances Cancer Immunity and Reduces Autoimmunity.
Cancer Res.,
July 15, 2006;
66(14):
7276 - 7284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tartz, J. Kamanova, M. Simsova, P. Sebo, S. Bolte, V. Heussler, B. Fleischer, and T. Jacobs
Immunization with a Circumsporozoite Epitope Fused to Bordetella pertussis Adenylate Cyclase in Conjunction with Cytotoxic T-Lymphocyte-Associated Antigen 4 Blockade Confers Protection against Plasmodium berghei Liver-Stage Malaria
Infect. Immun.,
April 1, 2006;
74(4):
2277 - 2285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
