Multidrug Resistance 1 Gene Transfer Can Confer Chemoprotection to Human Peripheral Blood Progenitor Cells Engrafted in Immunodeficient Mice
- 20 January 2002
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 13 (2) , 233-242
- https://doi.org/10.1089/10430340252769761
Abstract
Myelosuppression is the main side effect of cancer chemotherapy. An improved rate of retroviral vector-mediated gene transfer to hematopoietic stem cells, shown in more recent clinical trials, has created the basis to test the concept of myeloprotective gene therapy. We transplanted clinical-scale human peripheral blood progenitor cell grafts (n = 2) transduced with retroviral vector SF91m3, which contains the human multidrug resistance 1 gene (MDR1), into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Engrafted mice of one cohort were protected from paclitaxel toxicity (p < 0.05) and we noted a similar trend in the second cohort. In paclitaxel-treated mice that had received gene-transduced cells we found a significant increase in gene marking (p < 0.05 - p < 0.01) or P-glycoprotein expression (p < 0.01) compared with their chemotherapy-naive counterparts. This is the first report showing that cytostatic drug resistance gene therapy can mediate chemoprotection of human clinically relevant stem cell populations with marrow engraftment potential.Keywords
This publication has 44 references indexed in Scilit:
- Improved post-transcriptional processing of an MDR1 retrovirus elevates expression of multidrug resistance in primary human hematopoietic cellsGene Therapy, 2001
- MDR1 Gene Expression in NOD/SCID Repopulating Cells after Retroviral Gene Transfer under Clinically Relevant ConditionsMolecular Therapy, 2000
- Addition of the Human Interferon β Scaffold Attachment Region to Retroviral Vector Backbones Increases the Level ofin VivoTransgene Expression among Progeny of Engrafted Human Hematopoietic Stem CellsHuman Gene Therapy, 2000
- Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 DiseaseScience, 2000
- Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphomaGene Therapy, 1998
- Frequency Analysis ofMultidrug Resistance-1 Gene Transfer into Human Primitive Hematopoietic Progenitor Cells Using the Cobblestone Area-Forming Cell Assay and Detection of Vector-Mediated P-Glycoprotein Expression by Rhodamine-123Human Gene Therapy, 1996
- Bone marrow extracellular matrix molecules improve gene transfer into human hematopoietic cells via retroviral vectors.Journal of Clinical Investigation, 1994
- Improved Methods of Retroviral Vector Transduction and Production for Gene TherapyHuman Gene Therapy, 1994
- Engraftment of Immune-Deficient Mice with Human Hematopoietic Stem CellsScience, 1988
- The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and FunctionScience, 1988