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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Anderson WF. Human gene therapy. Science 256:808–813;1992.
Cepko C, Roberts BE, Mulligan RC. Construction and application of a highly transmissible murine retrovirus shuttle vector. Cell 37:1053–1062;1984.
Culver KW, Ram Z, Wallbridge S, Ishii H, Oldfield EH, Blaese RM. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 256:1550–1552;1992.
Dorshkind K, Pollock SB, Bosman MJ, Phillips RAJ. Natural killer (NK) cells are present in mice with severe combined immunodeficiency (SCID). J Immunol 134:3798–3801;1985.
Enrietto PJ, Payne LN, Hayman MJ. A recovered avian myelocytomatosis virus that induces lymphomas in chickens: Pathogenic properties and their molecular basis. Cell 35:369–379;1983.
Fosta O, Hansen CT, Cannon GB, Statham CN, Lichtenstein GR, Boyd MR. Lack of correlation between natural killer activity and tumor growth control in nude mice with different immune defects. Cancer Res 44:4403–4408;1984.
Kamel-Reid S, Dick JE. Engraftment of immune-deficient mice with human hematopoietic stem cells. Science 242:1706–1709;1988.
Love JM, Knight AM, McAleer MA, Todd JA. Towards construction of a high resolution map of the mouse genome using PCR-analyzed microsatellites. Nucleic Acids Res 18:4123–4130;1990.
Markowitz D, Goff S, Bank A. Construction and use of a safe and efficient amphotropic packaging cell line. Virology 167:400–406;1988.
McCune JM, Namikawa R, Kaneshima H, Schultz LD, Lieberman M, Weissman IL. The SCID-hu mouse:murine model for analysis of human hematolymphoid differentiation and function. Science 241:1632–1639;1988.
Miller AD. Human gene therapy comes of age. Nature 357:455–460;1992.
Mosier DE, Gulizia RJ, Baird SM, Wilson DB. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256–259;1988.
Tung FYT, Daniel MD. Targeted inhibition of immunodeficiency virus replication in lymphocytes through retroviral mediated gene transfer. Arch Virol 133:407–421;1993.
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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
- Retroviral vector
- Gene therapy
- SCID mice