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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bollard, C. M. Articles by Rooney, C. M. Search for Related Content PubMed PubMed Citation Articles by Bollard, C. M. Articles by Rooney, C. M. Related Collections Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2002, Vol. 99, No. 9, pp. 3179-3187 GENE THERAPY Adapting a transforming growth factor -related tumor protection strategy to enhance antitumor immunity Catherine M. Bollard, Claudia Rössig, M. Julia Calonge, M. Helen Huls, Hans-Joachim Wagner, Joan Massague, Malcolm K. Brenner, Helen E. Heslop, and Cliona M. Rooney From the Center for Cell and Gene Therapy, Departments of Pediatrics, Molecular Virology and Microbiology, and Medicine, Baylor College of Medicine, Houston, TX; and Memorial Sloan Kettering Cancer Center, New York, NY. Transforming growth factor  (TGF-), a pleiotropic cytokine that regulates cell growth and differentiation, is secreted by many human tumors and markedly inhibits tumor-specific cellular immunity. Tumors can avoid the differentiating and apoptotic effects of TGF- by expressing a nonfunctional TGF- receptor. We have determined whether this immune evasion strategy can be manipulated to shield tumor-specific cytotoxic T lymphocytes (CTLs) from the inhibitory effects of tumor-derived TGF-. As our model we used Epstein-Barr virus (EBV)-specific CTLs that are infused as treatment for EBV-positive Hodgkin disease but that are vulnerable to the TGF- produced by this tumor. CTLs were transduced with a retrovirus vector expressing the dominant-negative TGF- type II receptor HATGF-RII-cyt. HATGF-RII-cyt- but not green fluorescence protein (eGFP)-transduced CTLs was resistant to the antiproliferative and anticytotoxic effects of exogenous TGF-. Additionally, receptor-transduced cells continued to secrete cytokines in response to antigenic stimulation. TGF- receptor ligation results in phosphorylation of Smad2, and this pathway was disrupted in HATGF-RII-cyt-transduced CTLs, confirming blockade of the signal transduction pathway. Long-term expression of TGF-RII-cyt did not affect CTL function, phenotype, or growth characteristics. Tumor-specific CTLs expressing HATGF-RII-cyt should have a selective functional and survival advantage over unmodified CTLs in the presence of TGF--secreting tumors and may be of value in treatment of these diseases. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kim, G. Buchlis, Z. G. Fridlender, J. Sun, V. Kapoor, G. Cheng, A. Haas, H. K. Cheung, X. Zhang, M. Corbley, et al. Systemic Blockade of Transforming Growth Factor-{beta} Signaling Augments the Efficacy of Immunogene Therapy Cancer Res., December 15, 2008; 68(24): 10247 - 10256. [Abstract] [Full Text] [PDF] M. Zhang, B. E. Berndt, J.-J. Chen, and J. Y. Kao Expression of a Soluble TGF-{beta} Receptor by Tumor Cells Enhances Dendritic Cell/Tumor Fusion Vaccine Efficacy J. Immunol., September 1, 2008; 181(5): 3690 - 3697. [Abstract] [Full Text] [PDF] A. Wallace, V. Kapoor, J. Sun, P. Mrass, W. 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