Cytokine therapy with gene-transfected cells: single injection of
irradiated granulocyte-macrophage colony-stimulating factor-transduced
cells accelerates hematopoietic recovery after cytotoxic chemotherapy in
mice
FM Rosenthal, R Fruh, R Henschler, H Veelken, P Kulmburg, A Mackensen, B Gansbacher, R Mertelsmann and A Lindemann
Department of Medicine I (Haematology/Oncology), University Medical Center
Freiburg, Freiburg, Germany.
Development of cell-based delivery systems that can release therapeutic
levels of hematopoietic growth factors into the systemic circulation would
facilitate treatment of patients requiring cytokine therapy. In this study,
we have investigated the potential of granulocyte- macrophage
colony-stimulating factor (GM-CSF)-secreting, irradiated syngeneic murine
cells to accelerate hematopoietic recovery after cytotoxic chemotherapy. As
a model, CMS-5 fibrosarcoma cells, were transduced with a retroviral vector
containing the murine GM-CSF cDNA. Transduced cells secreted 38 ng
GM-CSF/10(6) cells in 24 hours. After irradiation, in vitro GM-CSF
production initially increased up to fivefold and was measurable for about
2 weeks. One and 2 days after injection of irradiated, GM-CSF-secreting
CMS-5 cells (N2/CMVGM- CSF/CMS5 # 6 cells) into mice, GM-CSF serum levels
of 405 +/- 58 pg/mL and 183 +/- 36 pg/mL were measured, respectively. Serum
levels were comparable with levels detected 3 hours after injection of 100
ng recombinant murine GM-CSF (rmGM-CSF) subcutaneously (90 pg/mL).
Injection of N2/CMVGM-CSF/CMS5 # 6 cells in cyclophosphamide-treated mice
was as effective in accelerating neutrophil recovery as twice daily
subcutaneous injections of rmGM-CSF. These data suggest that irradiated
hematopoietic growth factor-secreting cells might offer an alternative to
parenteral injections of recombinant cytokines in the treatment of
neutropenic patients.
Volume 84,
Issue 9,
pp. 2960-2965,
11/01/1994
Copyright © 1994 by The American Society of Hematology
