This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lillo, R. Articles by García-Sánchez, F. Search for Related Content PubMed PubMed Citation Articles by Lillo, R. Articles by García-Sánchez, F.

Efficient and Nontoxic Adenoviral Purging Method for Autologous Transplantation in Breast Cancer Patients¹

Laboratorio de Histocompatibilidad y Biología Molecular, Centro de Transfusión de Madrid, 28009 Madrid [R. L., A. A., S. S., J. F. d. V., M. J. A., A. B., J. L. V., F. G-S.]; Programa de Terapia Génica Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas/Marcelino Botín, 28040 Madrid [M. R., J. G-C., J. A. B.]; Unidad de Investigación. Hospital Niño Jesús, 28009 Madrid [M. R.]; and Unidad de Trasplante de Médula Ósea, Hospital Gregorio Marañón, 28009 Madrid [A. G-P., J. L. D.], Spain

Tumor cell contamination of clinical grafts is a major concern in autologous hematopoietic stem cell transplantation because these contaminating cells can contribute to relapse. In the present work, we use a suicide gene therapy approach that successfully accomplishes the two main goals of any purging strategy: highly efficient elimination of contaminating tumor cells and preservation of the engraftment capability of the hematopoietic progenitor cells. Human CD34⁺ cells spiked with breast cancer cells were infected with an adenoviral vector encoding the cytosine deaminase transgene (Ad-CMV-CD). In vitro, transduction with Ad-CMV-CD followed by exposure to 400 µM 5-fluorocytosine resulted in complete elimination of clonogenic contaminating tumor cells without affecting the clonogenic potential of the human hematopoietic CD34⁺ cells. Transplantation of nonobese diabetic/LtSz-scid/severe combined immunodeficient (NOD/SCID) mice with nonpurged contaminated grafts and purged contaminated grafts, allowed us to test the safety and efficacy of our procedure in two independent purging experiments. Hematopoietic engraftment kinetics as well as the quantity and quality of human engraftment were not affected by the purging therapy. Results showed a significant difference in survival between the nonpurged group (28%) and the purged group (100%; P = 0.012). Moreover, highly sensitive histological and molecular analyses confirmed the absence of tumor cells in the recipients of purged marrow. In contrast, metastatic tumors were detected in animals that received nonpurged grafts. We anticipate that this strategy will result in a safe and efficacious hematopoietic graft product for autologous transplantation for patients with multiple forms of epithelial cancers.

This article has been cited by other articles:

				C. M. Thirukkumaran, J. M. Luider, D. A. Stewart, T. Cheng, S. M. Lupichuk, M. J. Nodwell, J. A. Russell, I. A. Auer, and D. G. Morris Reovirus oncolysis as a novel purging strategy for autologous stem cell transplantation Blood, July 1, 2003; 102(1): 377 - 387. [Abstract] [Full Text] [PDF]