Engraftment of MDR1 and NeoR Gene-Transduced Hematopoietic Cells After Breast Cancer Chemotherapy

To determine whether the multidrug resistance gene MDR1could act as a selectable marker in human subjects, we studied engraftment of peripheral blood progenitor cells (PBPCs) transduced with either MDR1 or the bacterial NeoR gene in six breast cancer patients. This study differed from previous MDR1...

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Published inBlood Vol. 94; no. 1; pp. 52 - 61
Main Authors Moscow, Jeffrey A., Huang, Hui, Carter, Charles, Hines, Kenneth, Zujewski, JoAnne, Cusack, Georgie, Chow, Cathy, Venzon, David, Sorrentino, Brian, Chiang, Yawen, Goldspiel, Barry, Leitman, Susan, Read, Elizabeth J., Abati, Andrea, Gottesman, Michael M., Pastan, Ira, Sellers, Stephanie, Dunbar, Cynthia, Cowan, Kenneth H.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.07.1999
Subjects
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
Breast Neoplasms - genetics
Breast Neoplasms - physiopathology
Breast Neoplasms - therapy
Cell Differentiation - genetics
Combined Modality Therapy
Female
Gene Transfer Techniques
Genes, Bacterial
Genes, Reporter
Genetic Therapy
Graft Survival
Hematopoiesis
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells - pathology
Hematopoietic Stem Cells - physiology
Humans
Middle Aged
Transplantation, Autologous
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Summary:To determine whether the multidrug resistance gene MDR1could act as a selectable marker in human subjects, we studied engraftment of peripheral blood progenitor cells (PBPCs) transduced with either MDR1 or the bacterial NeoR gene in six breast cancer patients. This study differed from previous MDR1 gene therapy studies in that patients received only PBPCs incubated in retroviral supernatants (no nonmanipulated PBPCs were infused), transduction of PBPCs was supported with autologous bone marrow stroma without additional cytokines, and a control gene (NeoR) was used for comparison with MDR1. Transduced PBPCs were infused after high-dose alkylating agent therapy and before chemotherapy with MDR-substrate drugs. We found that hematopoietic reconstitution can occur using only PBPCs incubated ex vivo, that theMDR1 gene product may play a role in engraftment, and that chemotherapy may selectively expand MDR1 gene-transduced hematopoietic cells relative to NeoR transduced cells in some patients.
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ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V94.1.52.413k35_52_61