The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow A correction has been published
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 Related articles in The JI
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cohen, C. J.
Right arrow Articles by Morgan, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cohen, C. J.
Right arrow Articles by Morgan, R. A.
The Journal of Immunology, 2005, 175: 5799-5808.
Copyright © 2005 by The American Association of Immunologists

Recognition of Fresh Human Tumor by Human Peripheral Blood Lymphocytes Transduced with a Bicistronic Retroviral Vector Encoding a Murine Anti-p53 TCR

Cyrille J. Cohen*, Zhili Zheng*, Regina Bray*, Yangbing Zhao*, Linda A. Sherman{dagger}, Steven A. Rosenberg* and Richard A. Morgan1,*

* Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and {dagger} Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

The p53 protein is markedly up-regulated in a high proportion of human malignancies. Using an HLA-A2 transgenic mouse model, it was possible to isolate high-avidity murine CTLs that recognize class I-restricted human p53 epitopes. We isolated the {alpha}- and {beta}-chain of a TCR from a highly avid murine CTL clone that recognized the human p53264–272 epitope. These genes were cloned into a retroviral vector that mediated high efficiency gene transfer into primary human lymphocytes. Efficiencies of >90% for gene transfer into lymphocytes were obtained without selection for transduced cells. The p53 TCR-transduced lymphocytes were able to specifically recognize with high-avidity, peptide-pulsed APCs as well as HLA-A2.1+ cells transfected with either wild-type or mutant p53 protein. p53 TCR-transduced cells demonstrated recognition and killing of a broad spectrum of human tumor cell lines as well as recognition of fresh human tumor cells. Interestingly, both CD8+ and CD4+ subsets were capable of recognizing and killing target cells, stressing the potential application of such a CD8-independent TCR molecule that can mediate both helper and cytotoxic responses. These results suggest that lymphocytes genetically engineered to express anti-p53 TCR may be of value for the adoptive immunotherapy of patients with a variety of common malignancies.


Related articles in The JI:

IN THIS ISSUE

The JI 2005 175: 5565-5566. [Full Text]  



This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
A. Shablak, R. E. Hawkins, D. G. Rothwell, and E. Elkord
T Cell-Based Immunotherapy of Metastatic Renal Cell Carcinoma: Modest Success and Future Perspective
Clin. Cancer Res., November 1, 2009; 15(21): 6503 - 6510.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. A. Johnson, R. A. Morgan, M. E. Dudley, L. Cassard, J. C. Yang, M. S. Hughes, U. S. Kammula, R. E. Royal, R. M. Sherry, J. R. Wunderlich, et al.
Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen
Blood, July 16, 2009; 114(3): 535 - 546.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. S. Chervin, J. D. Stone, P. D. Holler, A. Bai, J. Chen, H. N. Eisen, and D. M. Kranz
The Impact of TCR-Binding Properties and Antigen Presentation Format on T Cell Responsiveness
J. Immunol., July 15, 2009; 183(2): 1166 - 1178.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. R. Parkhurst, J. Joo, J. P. Riley, Z. Yu, Y. Li, P. F. Robbins, and S. A. Rosenberg
Characterization of Genetically Modified T-Cell Receptors that Recognize the CEA:691-699 Peptide in the Context of HLA-A2.1 on Human Colorectal Cancer Cells
Clin. Cancer Res., January 1, 2009; 15(1): 169 - 180.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. D. Santomasso, W. K. Roberts, A. Thomas, T. Williams, N. E. Blachere, M. E. Dudley, A. N. Houghton, J. B. Posner, and R. B. Darnell
A T cell receptor associated with naturally occurring human tumor immunity
PNAS, November 27, 2007; 104(48): 19073 - 19078.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
J. N. Kochenderfer and R. E. Gress
A Comparison and Critical Analysis of Preclinical Anticancer Vaccination Strategies
Experimental Biology and Medicine, October 1, 2007; 232(9): 1130 - 1141.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Hsu, S. A. Jones, C. J. Cohen, Z. Zheng, K. Kerstann, J. Zhou, P. F. Robbins, P. D. Peng, X. Shen, T. J. Gomes, et al.
Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene
Blood, June 15, 2007; 109(12): 5168 - 5177.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. J. Cohen, Y. F. Li, M. El-Gamil, P. F. Robbins, S. A. Rosenberg, and R. A. Morgan
Enhanced Antitumor Activity of T Cells Engineered to Express T-Cell Receptors with a Second Disulfide Bond
Cancer Res., April 15, 2007; 67(8): 3898 - 3903.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Zhao, M. R. Parkhurst, Z. Zheng, C. J. Cohen, J. P. Riley, L. Gattinoni, N. P. Restifo, S. A. Rosenberg, and R. A. Morgan
Extrathymic Generation of Tumor-Specific T Cells from Genetically Engineered Human Hematopoietic Stem Cells via Notch Signaling
Cancer Res., March 15, 2007; 67(6): 2425 - 2429.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Tang, M. Molina, and S. Amar
p53 Short Peptide (p53pep164) Regulates Lipopolysaccharide-Induced Tumor Necrosis Factor-{alpha} Factor/Cytokine Expression
Cancer Res., February 1, 2007; 67(3): 1308 - 1316.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. C. Yang and R. Childs
Immunotherapy for Renal Cell Cancer
J. Clin. Oncol., December 10, 2006; 24(35): 5576 - 5583.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. A. Johnson, B. Heemskerk, D. J. Powell Jr., C. J. Cohen, R. A. Morgan, M. E. Dudley, P. F. Robbins, and S. A. Rosenberg
Gene Transfer of Tumor-Reactive TCR Confers Both High Avidity and Tumor Reactivity to Nonreactive Peripheral Blood Mononuclear Cells and Tumor-Infiltrating Lymphocytes
J. Immunol., November 1, 2006; 177(9): 6548 - 6559.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
R. A. Morgan, M. E. Dudley, J. R. Wunderlich, M. S. Hughes, J. C. Yang, R. M. Sherry, R. E. Royal, S. L. Topalian, U. S. Kammula, N. P. Restifo, et al.
Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes
Science, October 6, 2006; 314(5796): 126 - 129.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. J. Cohen, Y. Zhao, Z. Zheng, S. A. Rosenberg, and R. A. Morgan
Enhanced Antitumor Activity of Murine-Human Hybrid T-Cell Receptor (TCR) in Human Lymphocytes Is Associated with Improved Pairing and TCR/CD3 Stability.
Cancer Res., September 1, 2006; 66(17): 8878 - 8886.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X.-F. Bai, J.-Q. Liu, P. S. Joshi, L. Wang, L. Yin, J. Labanowska, N. Heerema, P. Zheng, and Y. Liu
Different Lineages of P1A-Expressing Cancer Cells Use Divergent Modes of Immune Evasion for T-Cell Adoptive Therapy
Cancer Res., August 15, 2006; 66(16): 8241 - 8249.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.