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- Title
Development of a gene therapy based bone marrow purging system for leukemias.
- Authors
Weitao Huang; Weihong Tan; Qiu Zhong; Schwarzenberger, Paul
- Abstract
Although viable gene therapy based methods have been reported for the selective removal or purging of contaminating epithelial derived cancer cells from stem cell grafts, similar strategies for the purging of leukemia cells have been significantly less efficient. Hematopoietic cells are difficult targets for transduction with currently available vectors. Polylysine based molecular conjugate vectors (MCV) were previously found to effectively transduce both normal and malignant hematopoietic cells. A panel of human leukemia cell lines as well as CD34+ selected primary human hematopoietic progenitor cells (HPC) were tested for differential gene expression utilizing different promoters. Reporter gene expression under the control of RSV and SV40 promoters showed a 6-log fold increase in leukemia cells when compared to primary HPC. Using a polylysine based recombinant molecular conglomerate vector (recMCV) encoding the HSV-tk suicide gene under control of RSV, we demonstrated effective and specific cell killing in all leukemia cell lines as well as in primary human leukemia cells derived from chemotherapy refractory patients, while HPC survived under the same conditions at approximately 20% viability. These proof of principle experiments demonstrate that gene therapy technology could be utilized to successfully purge leukemia cells from HPC.Cancer Gene Therapy (2005) 12, 873–883. doi:10.1038/sj.cgt.7700848; published online 13 May 2005
- Subjects
LEUKEMIA treatment; GENE therapy; BONE marrow purging; HEMATOPOIETIC stem cells; CANCER treatment; GENE expression; CANCER cells
- Publication
Cancer Gene Therapy, 2005, Vol 12, Issue 11, p873
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700848