Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer
Birkholz K, Hombach A, Krug C, Reuter S, Kershaw M, Kämpgen E, Schuler G, Abken H, Schaft N, Dörrie J (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 16
Pages Range: 596-604
Journal Issue: 5
DOI: 10.1038/gt.2008.189
Abstract
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-γ (IFNγ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNFα). 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 autoaggression.
Authors with CRIS profile
Gerold Schuler
Lehrstuhl für Haut- und Geschlechtskrankheiten
Niels Schaft
Medizinische Fakultät
Jan Dörrie
Department of Dermatology
Involved external institutions
Germany (DE)
Australia (AU)How to cite
APA:
Birkholz, K., Hombach, A., Krug, C., Reuter, S., Kershaw, M., Kämpgen, E.,... Dörrie, J. (2009). Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer. Gene Therapy, 16(5), 596-604. https://doi.org/10.1038/gt.2008.189
MLA:
Birkholz, K., et al. "Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer." Gene Therapy 16.5 (2009): 596-604.
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