Efficient adenovirus-mediated gene transduction of normal and leukemic hematopoietic cells (original) (raw)
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- Published: 01 October 1997
Gene Therapy volume 4, pages 1093–1099 (1997)Cite this article
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Abstract
We evaluated the efficiency of adenovirus-mediated gene transfer into normal and malignant human hematopoietic cells. An E-1 and E-3 deleted, replication-defective recombinant Ad.RSVβgal vector was used and the transduction efficiency was studied at a multiplicity of infection of 13 p.f.u. per cell. Approximately 40–50% of normal monocytes were transduced, whereas purified normal resting T cells and B cells were resistant to infection. We showed that 50–80% of primary chronic myeloid leukemia cells (CML, n = 12) were efficiently transduced. In contrast to CML, successful transduction of resting primary chronic B lymphocytic leukemia cells required appropriate preactivation of targeted cells. A novel protocol for the efficient transduction of adenovirus into B-CLL cells was presented. We showed that anti-CD40 mAb or CD40 ligand acts in synergy with rhIL-4 to enable the transduction of approximately 50–75% of B-CLL cells (B-CLL, n = 6). Expression of β-galactosidase in transduced CML cells and B-CLL cells was detected for at least 15 days after transduction. The present studies underline the utility of adenovirus vectors for the construction of cytokine gene-modified tumor vaccines for the treatment of hematopoietic malignancies such as CML and B-CLL.
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Authors and Affiliations
- Department of Clinical Immunology, University Hospital, Biomedical Center, Uppsala University, Uppsala, Sweden
MR Huang, A Kallin & TH Tötterman - Department of Animal Physiology, Biomedical Center, Uppsala University, Uppsala, Sweden
M Olsson - Medical Genetics, Biomedical Center, Uppsala University, Uppsala, Sweden
U Pettersson
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- MR Huang
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Huang, M., Olsson, M., Kallin, A. et al. Efficient adenovirus-mediated gene transduction of normal and leukemic hematopoietic cells.Gene Ther 4, 1093–1099 (1997). https://doi.org/10.1038/sj.gt.3300499
- Received: 19 August 1996
- Accepted: 06 June 1997
- Issue Date: 01 October 1997
- DOI: https://doi.org/10.1038/sj.gt.3300499