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Retroviral producer cells cause sarcoma in severe combined immunodeficiency mice

Abstract

Direct in situ introduction of retroviral producer cells might provide a form of treatment for localized tumors. A possible undesirable consequence of this treatment could be uncontrolled proliferation of the injected producer cells. To test this possibility, severe combined immunodeficiency (SCID) mice were reconstituted with human peripheral blood lymphocytes which were marked with a retroviral vector using a coculture method. Although specific measures were taken to remove the possible contaminating producer cells, a high percentage of mice developed fibrosarcoma 2–6 weeks after reconstitution. We hypothesized that tumors arose from a small number of contaminating producer cells in the inoculum. Tumor cells were consistently DNA tetraploid, a characteristic of the producer cell line. DNA extracted from tumor tissue was found to contain the gene (neomycin phosphotransferase) used to mark the producer cell line. Furthermore, SCID mice injected with 1 × 104 producer cells developed tumors with analogous characteristics. This report indicates that the retroviral producer cell line is tumorigenic in immune-deficient animals.

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Tung, F.Y.T., Kelley, V.S. & Hendricks, J.B. Retroviral producer cells cause sarcoma in severe combined immunodeficiency mice. J Biomed Sci 2, 131–135 (1995). https://doi.org/10.1007/BF02253063

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Key Words

  • Retroviral vector
  • Gene therapy
  • SCID mice
  • Tumorigenesis