This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pollok, K. E.
Right arrow Articles by Williams, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pollok, K. E.
Right arrow Articles by Williams, D. A.

 Previous Article  |  Next Article 

J Virol, June 1998, p. 4882-4892, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

High-Efficiency Gene Transfer into Normal and Adenosine Deaminase-Deficient T Lymphocytes Is Mediated by Transduction on Recombinant Fibronectin Fragments

Karen E. Pollok,1 Helmut Hanenberg,1 Timothy W. Noblitt,1 Wendy L. Schroeder,1 Ikunoshin Kato,2 David Emanuel,1 and David A. Williams1,3,*

Section of Pediatric Hematology/Oncology, Herman B. Wells Center for Pediatric Research, Riley Hospital for Children,1 and Howard Hughes Medical Institute,3 Indiana University School of Medicine, Indianapolis, Indiana 46202-5525, and Biotechnology Research Laboratories, Takara Shuzo Company, Otsu, Shiga 520-21, Japan2

Received 15 December 1997/Accepted 11 March 1998

Primary human T lymphocytes are powerful targets for genetic modification, although the use of these targets in human gene therapy protocols has been hampered by low levels of transduction. We have shown previously that significant increases in the transduction of hematopoietic stem and progenitor cells with retroviral vectors can be obtained by the colocalization of the retrovirus and target cells on specific fibronectin (FN) adhesion domains (H. Hanenberg, X. L. Xiao, D. Dilloo, K. Hashino, I. Kato, and D. A. Williams, Nat. Med. 2:876-882, 1996). We studied the transfer of genes into primary T lymphocytes by using FN-assisted retroviral gene transfer. Activated T lymphocytes were infected for three consecutive days on the recombinant FN fragment CH-296 with a retroviral vector encoding the murine B7-1 protein. Transduced lymphocytes were analyzed for murine B7-1 expression, and it was found that under optimal conditions, 80 to 89% of the CD3+ lymphocytes were transduced. Gene transfer was predominantly augmented by the interaction between VLA-4 on the T lymphocytes and the FN adhesion site CS-1. Adenosine deaminase (ADA)-deficient primary T lymphocytes transduced on CH-296 with a retrovirus encoding murine ADA (mADA) exhibited levels of mADA activity severalfold higher than the levels of the endogenous human ADA protein observed in normal human T lymphocytes. Strikingly, the long-term expression of the transgene was dependent on the activation status of the lymphocytes. This approach will have important applications in human gene therapy protocols targeting primary T lymphocytes.

* Corresponding author. Mailing address: Herman B. Wells Center for Pediatric Research, 1044 W. Walnut St., Room 402, Indianapolis, IN 46202. Phone: (317) 274-8679. Fax: (317) 274-8679. E-mail: dwilliam{at}indyvax.iupui.edu.

J Virol, June 1998, p. 4882-4892, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Burns, W. R., Zheng, Z., Rosenberg, S. A., Morgan, R. A. (2009). Lack of specific {gamma}-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation. Blood 114: 2888-2899 [Abstract] [Full Text]  
  • Doubrovin, M. M., Doubrovina, E. S., Zanzonico, P., Sadelain, M., Larson, S. M., O'Reilly, R. J. (2007). In vivo Imaging and Quantitation of Adoptively Transferred Human Antigen-Specific T Cells Transduced to Express a Human Norepinephrine Transporter Gene. Cancer Res. 67: 11959-11969 [Abstract] [Full Text]  
  • Roth, A., Baerlocher, G. M., Schertzer, M., Chavez, E., Duhrsen, U., Lansdorp, P. M. (2005). Telomere loss, senescence, and genetic instability in CD4+ T lymphocytes overexpressing hTERT. Blood 106: 43-50 [Abstract] [Full Text]  
  • Yagi, H., Nomura, T., Nakamura, K., Yamazaki, S., Kitawaki, T., Hori, S., Maeda, M., Onodera, M., Uchiyama, T., Fujii, S., Sakaguchi, S. (2004). Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol 16: 1643-1656 [Abstract] [Full Text]  
  • Kreklau, E. L., Pollok, K. E., Bailey, B. J., Liu, N., Hartwell, J. R., Williams, D. A., Erickson, L. C. (2003). Hematopoietic expression of O6-methylguanine DNA methyltransferase-P140K allows intensive treatment of human glioma xenografts with combination O6-benzylguanine and 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular Cancer Therapeutics 2: 1321-1329 [Abstract] [Full Text]  
  • Pradip, D., Peng, X., Durden, D. L. (2003). Rac2 Specificity in Macrophage Integrin Signaling: POTENTIAL ROLE FOR Syk KINASE. J. Biol. Chem. 278: 41661-41669 [Abstract] [Full Text]  
  • Roth, A., Yssel, H., Pene, J., Chavez, E. A., Schertzer, M., Lansdorp, P. M., Spits, H., Luiten, R. M. (2003). Telomerase levels control the lifespan of human T lymphocytes. Blood 102: 849-857 [Abstract] [Full Text]  
  • Parry, R. V., Rumbley, C. A., Vandenberghe, L. H., June, C. H., Riley, J. L. (2003). CD28 and Inducible Costimulatory Protein Src Homology 2 Binding Domains Show Distinct Regulation of Phosphatidylinositol 3-Kinase, Bcl-xL, and IL-2 Expression in Primary Human CD4 T Lymphocytes. J. Immunol. 171: 166-174 [Abstract] [Full Text]  
  • Schaft, N., Willemsen, R. A., de Vries, J., Lankiewicz, B., Essers, B. W. L., Gratama, J.-W., Figdor, C. G., Bolhuis, R. L. H., Debets, R., Adema, G. J. (2003). Peptide Fine Specificity of Anti-Glycoprotein 100 CTL Is Preserved Following Transfer of Engineered TCR{alpha}{beta} Genes Into Primary Human T Lymphocytes. J. Immunol. 170: 2186-2194 [Abstract] [Full Text]  
  • Levings, M. K., Sangregorio, R., Sartirana, C., Moschin, A. L., Battaglia, M., Orban, P. C., Roncarolo, M.-G. (2002). Human CD25+CD4+ T Suppressor Cell Clones Produce Transforming Growth Factor {beta}, but not Interleukin 10, and Are Distinct from Type 1 T Regulatory Cells. JEM 196: 1335-1346 [Abstract] [Full Text]  
  • Lei, P., Bajaj, B., Andreadis, S. T. (2002). Retrovirus-Associated Heparan Sulfate Mediates Immobilization and Gene Transfer on Recombinant Fibronectin. J. Virol. 76: 8722-8728 [Abstract] [Full Text]  
  • Chames, P., Willemsen, R. A., Rojas, G., Dieckmann, D., Rem, L., Schuler, G., Bolhuis, R. L., Hoogenboom, H. R. (2002). TCR-Like Human Antibodies Expressed on Human CTLs Mediate Antibody Affinity-Dependent Cytolytic Activity. J. Immunol. 169: 1110-1118 [Abstract] [Full Text]  
  • Liu, K., Rosenberg, S. A. (2001). Transduction of an IL-2 Gene into Human Melanoma-Reactive Lymphocytes Results in Their Continued Growth in the Absence of Exogenous IL-2 and Maintenance of Specific Antitumor Activity. J. Immunol. 167: 6356-6365 [Abstract] [Full Text]  
  • Ragg, S., Xu-Welliver, M., Bailey, J., D’Souza, M., Cooper, R., Chandra, S., Seshadri, R., Pegg, A. E., Williams, D. A. (2000). Direct Reversal of DNA Damage by Mutant Methyltransferase Protein Protects Mice against Dose-intensified Chemotherapy and Leads to in Vivo Selection of Hematopoietic Stem Cells. Cancer Res. 60: 5187-5195 [Abstract] [Full Text]  
  • Dardalhon, V., Jaleco, S., Rebouissou, C., Ferrand, C., Skander, N., Swainson, L., Tiberghien, P., Spits, H., Noraz, N., Taylor, N. (2000). Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector. Blood 96: 885-893 [Abstract] [Full Text]  
  • Koehne, G., Gallardo, H. F., Sadelain, M., O'Reilly, R. J. (2000). Rapid selection of antigen-specific T lymphocytes by retroviral transduction. Blood 96: 109-117 [Abstract] [Full Text]  
  • Berger, C., Xuereb, S., Johnson, D. C., Watanabe, K. S., Kiem, H.-P., Greenberg, P. D., Riddell, S. R. (2000). Expression of Herpes Simplex Virus ICP47 and Human Cytomegalovirus US11 Prevents Recognition of Transgene Products by CD8+ Cytotoxic T Lymphocytes. J. Virol. 74: 4465-4473 [Abstract] [Full Text]  
  • MacNeill, E. C., Hanenberg, H., Pollok, K. E., van der Loo, J. C. M., Bierhuizen, M. F. A., Wagemaker, G., Williams, D. A. (1999). Simultaneous Infection with Retroviruses Pseudotyped with Different Envelope Proteins Bypasses Viral Receptor Interference Associated with Colocalization of gp70 and Target Cells on Fibronectin CH-296. J. Virol. 73: 3960-3967 [Abstract] [Full Text]  
  • Dao, M.A., Hashino, K., Kato, I., Nolta, J.A. (1998). Adhesion to Fibronectin Maintains Regenerative Capacity During Ex Vivo Culture and Transduction of Human Hematopoietic Stem and Progenitor Cells. Blood 92: 4612-4621 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»