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Lentiviral Vector Gene Transfer into Human T Cells

  • Protocol
Genetic Modification of Hematopoietic Stem Cells

Part of the book series: Methods In Molecular Biology™ ((MIMB,volume 506))

Summary

Efficient gene transfer into T lymphocytes may allow the treatment of several genetic dysfunctions of the hematopoietic system, such as severe combined immunodeficiency, and the development of novel therapeutic strategies for diseases such as cancers and acquired diseases such as AIDS. Lentiviral vectors can transduce many types of nonproliferating cells, with the exception of some particular quiescent cell types such as resting T cells. Completion of reverse transcription, nuclear import, and subsequent integration of the lentivirus genome do not occur in these cells unless they are activated via the T-cell receptor (TCR) and/or by cytokines inducing resting T cells to enter in G1b phase of the cell cycle. In T-cell-based gene therapy trials performed to date, cells have been preactivated via their cognate antigen receptor (TCR). However, TCR stimulation shifts the T cells from naïve to memory phenotype and leads to skewing of the T-cell population. Since, especially the naïve T cells will provide a long-lasting immune reconstitution to patients these are the cells that need to be transduced for effective gene therapy. Now it is clear that use of the survival cytokines, IL-2 or IL-7, allows an efficient lentiviral vector gene transfer and could preserve a functional T-cell repertoire while maintaining an appropriate proportion of naïve and memory T cells. In this protocol we give details on lentiviral transduction of T cells using TCR-stimulation or rIL-7 prestimulation. In addition, we describe the use of a new generation of lentiviral vectors displaying T-cell-activating ligands at their surface for targeted T-cell gene transfer.

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Acknowledgments

This work was supported by the Agence Nationale pour la Recherche contre le SIDA (ANRS), the European community (contract LSHB-CT-2004-005242, “Consert”), and INSERM. We acknowledge the contributions of Naomi Taylor, Louise Swainson, and Valerie Dardahlon to these studies.

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  1. Ecole Normale Superior Lyon, Lyon, France

    Els Verhoeyen, Caroline Costa & Francois-Loic Cosset

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  1. Els Verhoeyen
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  2. Caroline Costa
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  3. Francois-Loic Cosset
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  1. Department of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straβe 1, Hannover, 30625, Germany

    Christopher Baum

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Verhoeyen, E., Costa, C., Cosset, FL. (2009). Lentiviral Vector Gene Transfer into Human T Cells. In: Baum, C. (eds) Genetic Modification of Hematopoietic Stem Cells. Methods In Molecular Biology™, vol 506. Humana Press. https://doi.org/10.1007/978-1-59745-409-4_8

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  • DOI: https://doi.org/10.1007/978-1-59745-409-4_8

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