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Research Article Free access | 10.1172/JCI119072

Selective transgene expression for detection and elimination of contaminating carcinoma cells in hematopoietic stem cell sources.

L Chen, M Pulsipher, D Chen, C Sieff, A Elias, H A Fine, and D W Kufe

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Find articles by Chen, L. in: PubMed | Google Scholar

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Find articles by Pulsipher, M. in: PubMed | Google Scholar

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Find articles by Chen, D. in: PubMed | Google Scholar

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Find articles by Sieff, C. in: PubMed | Google Scholar

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Find articles by Elias, A. in: PubMed | Google Scholar

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Find articles by Fine, H. in: PubMed | Google Scholar

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Find articles by Kufe, D. in: PubMed | Google Scholar

Published December 1, 1996 - More info

Published in Volume 98, Issue 11 on December 1, 1996
J Clin Invest. 1996;98(11):2539–2548. https://doi.org/10.1172/JCI119072.
© 1996 The American Society for Clinical Investigation
Published December 1, 1996 - Version history
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Abstract

Tumor contamination of bone marrow (BM) and peripheral blood (PB) may affect the outcome of patients receiving high dose chemotherapy with autologous transplantation of hematopoietic stem cell products. In this report, we demonstrate that replication defective adenoviral vectors containing the cytomegalovirus (CMV) or DF3/MUC1 carcinoma-selective promoter can be used to selectively transduce contaminating carcinoma cells. Adenoviral-mediated reporter gene expression in breast cancer cells was five orders of magnitude higher than that found in BM, PB, and CD34+ cells. Our results demonstrate that CD34+ cells have low to undetectable levels of integrins responsible for adenoviral internalization. We show that adenoviral-mediated transduction of a reporter gene can detect one breast cancer cell in 5 x 10(5) BM or PB cells with a vector containing the DF3/MUC1 promoter. We also show that transduction of the HSV-tk gene for selective killing by ganciclovir can be exploited for purging cancer cells from hematopoietic stem cell populations. The selective expression of TK followed by ganciclovir treatment resulted in the elimination of 6-logs of contaminating cancer cells. By contrast, there was little effect on CFU-GM and BFU-E formulation or on long term culture initiating cells. These results indicate that adenoviral vectors with a tumor-selective promoter provide a highly efficient and effective approach for the detection and purging of carcinoma cells in hematopoietic stem cell preparations.

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