Gene-Therapy Based Purging System for Leukemias

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Original Article

Cancer Gene Therapy (2005) 12, 873–883. doi: 10.1038/sj.cgt.7700848;

published online 13 May 2005

Development of a gene therapy based bone marrow purging system for

leukemias

Weitao Huang1, Weihong Tan1, Qiu Zhong1 and Schwarzenberger1

1Gene Therapy Program, Louisiana State University Health Sciences

Center, New Orleans, Louisiana, USA

Correspondence: Dr P Schwarzenberger, MD, Louisiana State University

Health Sciences Center New Orleans, Department of Genetics and Gene

Therapy Program, 533 Bolivar St, CSRB Room 611, New Orleans, LA

70122, USA. E-mail: schwarzenberger@...

Received 08 November 2004; Published online 13 May 2005.

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.