HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A correction has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, C. J. Articles by Morgan, R. A. Search for Related Content PubMed PubMed Citation Articles by Cohen, C. J. Articles by Morgan, R. A.

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, Steven A. Rosenberg^* and Richard A. Morgan^1,*

^* Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and 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 - and -chain of a TCR from a highly avid murine CTL clone that recognized the human p53_264–272 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:

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]