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The impact of antigen expression in antigen-presenting cells on humoral immune responses against the transgene product

Gene Therapy volume 17, pages 288–293 (2010)Cite this article

Abstract

Treatment of genetic diseases by gene therapy is hampered by immune responses against the transgene product. Promoter choice has been shown to be an important parameter of the presence or absence of antibodies against the transgene product after gene transfer. Here, the generality of some of these observations was tested by comparing different murine strains and different transgene products. We show immunological unresponsiveness for human apolipoprotein (apo) A-I in six murine strains after transfer with E1E3E4-deleted adenoviral vectors containing hepatocyte-specific expression cassettes. However, differences in the induction of a humoral immune response against human apo A-I after gene transfer with vectors driven by the major histocompatibility complex class II Eβ promoter and the ubiquitously active cytomegalovirus promoter were not consistent in these six murine strains. Furthermore, use of a potent hepatocyte-specific expression cassette did not prevent a humoral immune response against human plasminogen in C57BL/6 mice. In contrast, human microplasminogen transfer resulted in stable expression in the absence of an immune response against the transgene product. Taken together, the molecular design of strategies to abrogate or induce an immune response against the transgene product may be hampered by the multitude of parameters affecting the outcome, thus limiting the external validity of results.

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Acknowledgements

This work was supported by Grants G.0564.05 and G.0533.08 of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen. The Center for Molecular and Vascular Biology is supported by the Excellentiefinanciering KU Leuven (EF/05/013). Frank Jacobs is a research assistant of the Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen. Eline Van Craeyveld is a research assistant of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen.

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  1. Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium

    Y Feng, F Jacobs, E Van Craeyveld, J Lievens, J Snoeys, S Van Linthout & B De Geest

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  1. Y Feng
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Correspondence to B De Geest.

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Feng, Y., Jacobs, F., Van Craeyveld, E. et al. The impact of antigen expression in antigen-presenting cells on humoral immune responses against the transgene product. Gene Ther 17, 288–293 (2010). https://doi.org/10.1038/gt.2009.125

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