Efficient adenovirus-mediated gene transduction of normal and leukemic hematopoietic cells
1997 (English)In: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 4, no 10, 1093-1099 p.Article in journal (Refereed) Published
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.RSV beta gal 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 beta-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.
Place, publisher, year, edition, pages
1997. Vol. 4, no 10, 1093-1099 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-57011PubMedID: 9415316OAI: oai:DiVA.org:uu-57011DiVA: diva2:84920