Skip to main content
Log in

Immunological regression of metastatic cancer in the liver as a result of “in vivo xenogenization”

  • Published:
Biotherapy

Abstract

We attempted to induce the regression of liver metastatic tumor cellsin vivo by the administration to rats of Friend leukemia virus (FV) (in vivo xenogenization). The virus which was used in this experiment, FV, is highly immunogenic and does not normally cause disease in an adult rat. At first, we induced a FV viremia in tumor bearing rats in order to deliver the virus to the site of the tumor cells. FV viremia was induced by injecting 60 mg/kg cyclophosphamide (CY) i.v. after the administration of FV, and by transferring syngeneic bone marrow cells so that FV would be able to infect them and then replicate.

In order that the tumor cells which were infected with virus should regress, it was necessary to break down their tolerance to FV antigens. As adoptive immunotherapy we therefore, transferred syngeneic spleen cells from rats which had been immunized with FV to tumor bearing rats. The result of this experiment was that these tumor bearing rats infected with FV which had received either normal syngeneic spleen cells or no spleen cells as controls died from liver metastasis (8 out of 9 rats (89%) and 15 out of 17 (88%) respectively). On the other hand, only 4 out of the 15 (27%) tumor bearing rats which were infected with FV and which received FV-immune spleen cells died from liver metastasis.

These sets of data indicate that thein vivo xenogenization of tumor cells are indeed able to induce the regression of metastic tumor cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

CY:

cyclophosphamide

FV:

Friend leukemia virus

MuLV:

murine leukemia virus

TAA:

tumor associated antigen

VAA:

virus associated antigen

References

  1. Kobayashi H, Sendo F, Shirai T, Kaji H, Kodama T, Saitoh H. Modification in growth of transplantable rat tumors exposed to Friend virus. J Natl Cancer Inst, 1969; 42: 413–9.

    PubMed  Google Scholar 

  2. Kobayashi H, Kodama T, Shirai T, Kaji H, Hosokawa M, Sendo F, Saitoh H, Takeichi N. Artificial regression of rat tumor infected with Friend virus (xenogenization)—An effect produced by acquired antigen. Hokkaido J Med Sci 1969; 44: 133–4.

    Google Scholar 

  3. Kobayashi H, Kuzumaki N, Gotohda E, Takeichi N, Sendo F, Hosokawa M, Kodama T. Specific antigenicity of tumors and immunological tolerance in the rat induced by Friend, Gross, and Rauscher viruses. Cancer Res 1973; 33: 1589–1603.

    Google Scholar 

  4. Kobayashi H, Sendo F, Shirai T, Takeichi N, Hosokawa M, Kodama T. Inhibition of transplantable rat tumor by immunization with identical tumor cells infected with Friend virus. J Natl Cancer Inst 1970; 44: 11–19.

    PubMed  Google Scholar 

  5. Kobayashi H, Kodama T, Gotohda E. Xenogenization of tumor cells. Hokkaido Univ Med Libr Series, Sapporo 1977; 9: 1–24.

    Google Scholar 

  6. Kobayashi H, Sendo F. Immunogenicity of viable xenogenized tumor cells. GANN Monogr Cancer Res 1979; 23: 27–39.

    Google Scholar 

  7. Kobayashi H. Viral xenogenization of intact tumor cells Advance in Cancer Res 1979; 30: 270–99.

    Google Scholar 

  8. Kodama T, Gotohda E, Kobayashi H. Immuno-electron microscopic studies on surface antigens of rat tumor cells infected with Friend virus. GANN 1973; 64: 475–9.

    PubMed  Google Scholar 

  9. Kodama T, Kato H, Gotohda E, Kobayashi H, Sendo F. Regression of established tumors in rats by injection of diethylaminoethyl-dextran and Friend murine leukemia virus. J Natl Cancer Inst 1978; 61: 403–6.

    PubMed  Google Scholar 

  10. Chenaille D, Davy JP, Tabitian A, Bairon M. Routine method for concentration and partial purification of murine leukemia virus (Rauscher). Nature (Lond.) 1967; 213: 107–9.

    Google Scholar 

  11. Axelrad AA, Steeves RA. Assay for Friend leukemia virus: Rapid quantitative method based on enumeration of macroscopic spleen foci in mice. Virology 1964; 24: 513–8.

    PubMed  Google Scholar 

  12. Kuzumaki N, Kobayashi H. Cell surface antigens induced by Friend and Rauscher virus complexes and their associated lymphatic leukemia virus in the rat. Cancer Res 1975; 35: 1718–22.

    PubMed  Google Scholar 

  13. Takeichi N, Kuzumaki N, Kobayashi H. Immunological studies of runting syndrome in rats inoculated with Friend virus. Cancer Res 1973; 33: 3096–3102.

    PubMed  Google Scholar 

  14. Takeichi N, Kaji H, Kodama T, Kobayashi H. Breakdown of Friend virus-induced tolerance and development of runting syndrome in rats. Cancer Res 1974; 34: 543–50.

    PubMed  Google Scholar 

  15. Takeichi N, Kobayashi H. Development of runting syndrome in Friend and Gross virus-induced doubly tolerant rats. Cancer Res 1980; 40: 448–51.

    PubMed  Google Scholar 

  16. Takeichi N, Kuzumaki N, Kodama T, Kobayashi H, Boone CW. Adoptive immunotherapy of a Gross virus producing lymphoma and a methylocholanthrene-induced fibrosarcoma in tolerant rats. Cancer Res 1976; 36: 4039–43.

    PubMed  Google Scholar 

  17. Takeichi N, Kobayashi H. Breakdown of MuLV-induced tolerance and subsequent regression of xenogenized tumors. GANN Monogr, Cancer Res 1979; 23: 97–108.

    Google Scholar 

  18. Iglehart JD, Ward EC, Thiel K, Huper G, Geler SS, Bolognesi DP.In vivo antigenic modulation of tumor cells. I. Introduction of murine leukemia virus antigens on non-virus-producing murine sarcomas. J Natl Cancer Inst 1981; 67: 107–15.

    PubMed  Google Scholar 

  19. Iglehart JD, Ward WC, Huper G, Thiel K, Bolognesl DP.In vivo antigenic modulation of tumor cells. II. Distribution of virus in sarcoma-bearing mice. J Natl Cancer Inst 1981; 67: 117–22.

    PubMed  Google Scholar 

  20. Lagrange PH, Mackaness GB, Miller TE. Potentiation of T cell-mediated immunity by selective suppression of antibody formation with cyclophosphamide. J Exp Med 1974; 139: 1529–39.

    PubMed  Google Scholar 

  21. Turk JL, Parker D. Further studies on B-lymphocyte suppression in delayed hypersensitivity, indicating a possible mechanism for Jones-Mote hypersensitivity. Immunol 1973; 24: 751–8.

    Google Scholar 

  22. Aisenberg AC, Murray C. Cell transfer studies in cyclophosphamide-induced tolerance. Cell Immunol 1973; 7: 143–51.

    PubMed  Google Scholar 

  23. Frish AW, Davies GH. Inhibition of hemagglutinin synthesis by cytoxan: Specificity and drug-induced ‘tolerance’. J Lab Clin Med 1966; 68: 103–12.

    PubMed  Google Scholar 

  24. Lin H. Differential lethal effect of cytotoxic agents on proliferating and nonproliferating lymphoid cells. Cancer Res 1973; 33: 1716–20.

    PubMed  Google Scholar 

  25. Many A, Schwartz RZ. Drug-induced immunologic tolerance: Site of action of cyclophosphamide. Proc Soc Exp Biol Med 1970; 133: 754–7.

    PubMed  Google Scholar 

  26. Many A, Schwartz RZ. On the mechanism of immunological tolerance in cyclophosphamide-treated mice. Clin Exp Immunol 1970; 6: 87–99.

    PubMed  Google Scholar 

  27. Shand FL, Howard JG. Cyclophosphamide inhibited B-cell receptor regeneration as a basis for drug-induced tolerance. Nature 1978; 271: 255–7.

    PubMed  Google Scholar 

  28. Takeichi N. Comparative studies of immunological disorders in rat infected with Friend or Gross virus. Acta Path Jap 1973; 23: 953–62.

    PubMed  Google Scholar 

  29. Turk JL, Poulter LW. Selective depletion of lymphoid tissue by cyclophosphamide. Clin Exp Immunol 1972; 10: 285–96.

    PubMed  Google Scholar 

  30. Winkelstein A. Mechanisms of immunosuppresssvn: Effects of cyclophosphamide on cellular immunity. Blood 1973; 41: 273–84.

    PubMed  Google Scholar 

  31. Winkelstein A. Effect of immunosuppressive drugs on T and B-lymphocytes in guinea pigs. Blood 1977; 50: 81–91.

    PubMed  Google Scholar 

  32. Bennet M, Steeve RA. Immunocompetent cell functions in mice infected with Friend leukemia virus. J Natl Cancer Inst 1970; 44: 1107–19.

    PubMed  Google Scholar 

  33. Mizushima Y, Sendo F, Takeichi N, Hosokawa M, Kobayashi H. Enhancement of antitumor transplantaion resistance in rats by appropriately timed administration of busulfan. Cancer Res 1981; 41: 2917–21.

    PubMed  Google Scholar 

  34. Morikawa K, Hosokawa M, Hamada J, Xu Z-y, Kobayashi H. Possible participation of tumoricidal macrophages in therapeutic effect of bleomycin on a transplantable rat fibrosarcoma. Cancer Res 1986; 46: 684–8.

    PubMed  Google Scholar 

  35. Kasai M, Yamaguchi H, Hosokawa M, Mizushima Y, Kobayashi H. Increased sensitivity of murine leukemia virus-infected tumor cells to lymphoyte-mediated cytotoxicity. J Natl Cancer Inst 1981; 67: 417–22.

    PubMed  Google Scholar 

  36. Morikawa K, Hamada J, Itaya T, Ishikawa M, Takeichi N, Hosokawa M, Kobayashi H. Modification of regression of virally xenogenized tumor cells by cyclophosphamide and busulfan. Cancer Immunol Immunother 1988; 26: 18–22.

    PubMed  Google Scholar 

  37. Okayasu T, Morita T, Itaya T, Hosokawa M, Tanabe T, Kobayashi H. The role of antibody producing cells in regression. Proc Jpn Cancer Assoc 1986; 45: 385.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suzuki, Y., Okayasu, T., Morikawa, K. et al. Immunological regression of metastatic cancer in the liver as a result of “in vivo xenogenization”. Biotherapy 2, 41–49 (1990). https://doi.org/10.1007/BF02172075

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02172075

Key words

Navigation