Journal
GENE THERAPY
Volume 16, Issue 5, Pages 596-604Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2008.189
Keywords
RNA transfection; retroviral gene transfer; chimeric TCR; immunoreceptor
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Funding
- Friedrich-Alexander-University Erlangen-Nuremberg [DE-07.09.12.1]
- DFG-German Research Foundation [SCHA 1247/1-1]
- European Community
- Fortune program of the Medical Faculty
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Human T lymphocytes can be redirected with a new defined specificity by expression of a chimeric T-cell receptor (immunoreceptor) for the use in adoptive immunotherapy of cancer. Whereas standard procedures use retroviral gene transduction to constitutively express immunoreceptors in T cells, we here explored for the first time mRNA electroporation to achieve transient immunoreceptor expression, and thereby minimizing the risk of persistence of potential autoaggression. CD4(+) and CD8(+) T cells were efficiently transfected with immunoreceptors specific for ErbB2 and CEA. The immunoreceptor expression was transient with half-maximal expression at day 2 and no detectable immunoreceptor expression at day 9 after electroporation. Immunoreceptor-transfected T cells were specifically activated upon coincubation with ErbB2(+) and CEA(+) tumor cells, respectively, resulting in secretion of interferon-gamma (IFN gamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF alpha). Furthermore, immunoreceptor-transfected CD8(+) T cells specifically lysed ErbB2(+) and CEA(+) tumor cells, respectively. The RNA-transfected T cells retained their cytotoxic function after 2 days of activation and exhibited cytolytic activities like retrovirally transduced T cells. RNA electroporation of T cells thereby provides a versatile tool for transient immunoreceptor expression, which may be of advantage in avoiding the persistence of unintended auto-aggression. Gene Therapy (2009) 16, 596-604; doi: 10.1038/gt.2008.189; published online 22 January 2009
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