Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 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.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Table and Figure
Right arrow All Versions of this Article:
2005-06-2298v1
106/9/3127    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lute, K. D.
Right arrow Articles by Liu, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lute, K. D.
Right arrow Articles by Liu, Y.
Related Collections
Right arrow Immunobiology
Right arrow Neoplasia
Right arrow Immunotherapy
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

IMMUNOBIOLOGY

Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti–CTLA-4 antibodies

Kenneth D. Lute, Kenneth F. May, Jr, Ping Lu, Huiming Zhang, Ergun Kocak, Bedrick Mosinger, Christopher Wolford, Gary Phillips, Michael A. Caligiuri, Pan Zheng, and Yang Liu

From the Division of Cancer Immunology, the Department of Pathology, the Center for Biostatistics, the Neurobiotechnology Center, and the Department of Internal Medicine, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH.

Although results from preclinical studies in animal models have proven the concept for use of anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies in cancer immunotherapy, 2 major obstacles have hindered their successful application for human cancer therapy. First, the lack of in vitro correlates of the antitumor 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 2 issues, we have generated human CTLA4 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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 JEMHome page
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]

Home page
 NEJMHome page
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]

Home page
 BloodHome page
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]

Home page
 Cancer Res.Home page
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]

Home page
 Infect. Immun.Home page
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]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020