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

The Journal of Clinical Investigation
L ChenD W Kufe

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 formul...Continue Reading

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Citations

May 1, 1997·Lancet·R R Weichselbaum, D Kufe
Jul 13, 2000·Human Gene Therapy·S Halene, D B Kohn
Apr 21, 2001·DNA and Cell Biology·J R Morris, J Taylor-Papadimitriou
Feb 23, 2000·Journal of Virology·D M ShayakhmetovA Lieber
Nov 3, 2011·Bone Marrow Research·Chandini M Thirukkumaran, Don G Morris
Sep 15, 2004·European Journal of Pharmacology·Anas El-Aneed
Mar 10, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marcus NilssonXiaolong Fan
May 23, 2001·Leukemia·V F Van TendelooZ N Berneman
Apr 24, 2007·Bone Marrow Transplantation·C M ThirukkumaranD G Morris
May 14, 2005·Cancer Gene Therapy·Weitao HuangPaul Schwarzenberger
May 14, 2010·Postgraduate Medicine·Mark TangneyGerald C O'Sullivan
Jan 1, 2019·Current Pathobiology Reports·Nancy Y Villa, Grant McFadden
Mar 5, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roisin M DwyerJohn C Morris
Mar 12, 2021·Current Oncology·Vanessa InnaoAlessandro Allegra
Feb 24, 2001·The American Journal of the Medical Sciences·P SchwarzenbergerJ K Kolls

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