Summary
We have tested the effects of specific and nonspecific immunostimulation on the spontaneous regression and recurrence of erythroleukemia induced by a strain of the Friend murine leukemia virus complex, RFV. Subcutaneous inoculation of mice with UV-irradiated allogeneic leukemic spleen cells (LSC) protected against subsequent virus challenge. RFV-leukemic mice injected with LSC into subcutaneous BCG-primed sites had a significantly increased incidence of leukemia regression. When leukemic mice received BCG or LSC alone or normal allogeneic spleen cells (NSC) in place of LSC the incidence of regression was not different from that recorded in untreated controls. A single treatment of recently regressed mice with LSC given into BCG-primed sites prolonged the disease-free period, while LSC alone, BCG alone, or NSC had no such effect. Our data support an immunological basis for spontaneous regression of erythroleukemia and for maintenance of the regressed state. This system provides a model for testing the efficacy of immunotherapeutic protocols for maintenance of leukemia remission and tumor dormancy.
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Aaronson, S. A.: Common genetic alterations of RNA tumor viruses grown in human cells. Nature 230, 445 (1971)
Axelrad, A., Steeves, R. A.: Assay for Friend leukemia virus: Rapid quantification method based on enumeration of macroscopic spleen foci in mice. Virology 24, 513 (1964)
Axelrad, A., Thomson, S.: Radiosensitivity and growth of Friend leukemia virus studied with the spleen focus assay method. Int. J. Cancer 4, 179 (1969)
Blanden, R. V., Lefford, M. J., Mackness, G. B.: The host response to Calmette-Guérin Bacillus infection in mice. J. Exp. Med. 129, 1079 (1969)
Cerny, J., Essex, M., Rich, M. A., Hardy, W. D.: Expression of virus associated antigens and immune cell functions during spontaneous regression of Friend viral murine leukemia. Int. J. Cancer 15, 351 (1975)
Dietz, M., Furmanski, P., Clymer, R., Rich, M. A.: Effects of thymectomy and antithymocyte serum in spontaneous regression of Friend virus induced erythroleukemia. J. Natl. Cancer Inst. 57, 91 (1976)
Dietz, M., Longley, C., Fouchey, S. P., Hall, L., Rich, M. A., Furmanski, P.: Spontaneous regression of Friend virus-induced erythroleukemia. II. Regression of Friend murine leukemia virus-induced lymphocytic leukemia. J. Natl. Cancer Inst. 59, 957 (1977)
Doft, B. H., Merchant, B., Johannessen, L., Chaparas, S. D., Sher, N. A.: Contrasting effects of BCG on spleen and lymph node antibody responses in nude and normal mice. J. Immunol. 117, 1638 (1976)
Dupuy, J. M., Kourilsky, F. M., Fradelizzi, D., Feingold, N., Jacquillat, C. L., Bernard, J., Dausset, J.: Depression of immunological reactivity of patients with acute leukemia. Cancer 27, 323 (1971)
Gray, D. F., Jennings, P. A.: Allergy in experimental mouse tuberculosis. Annu. Rev. Tuberc. 72, 171 (1955)
Greene, W. H., Schimpff, S. C., Wiernik, P. H.: Cell-mediated immunity in acute nonlymphocytic leukemia: Relationship to host factors, therapy, and prognosis. Blood 43, 1 (1974)
Gutterman, J. U., Rosen, R. D., Butler, K. B., McCredie, K. B., Bodey, G. P., Freireich, E. J., Hersch, E. M.: Immunoglobulin on tumor cells and tumor induced lymphocyte blastogenesis in human acute leukemia. N. Engl. J. Med. 288, 169 (1973)
Gutterman, J. V., Mavligit, G. M., Burgess, M. A., Cardemas, J. O., Blumenschein, J. A., Gottlieb, J. A., McBride, C. M., McCredie, K. B., Bodey, G. P., Rodriguez, V., Freireich, E. J., Hersh, E. M.: Immunotherapy of breast cancer, malignant melanoma, and acute leukemia with BCG: Prolongation of disease free interval and survival. Cancer Immunol. Immunother. 1, 99 (1976)
Hawrylko, E., Mackaness, G. B.: Immunopotentiation with BCG. IV. Factors affecting the magnitude of an antitumor response. J. Natl. Cancer Inst. 51, 1683 (1973)
Heding, L. D., Schaller, J. P., Blakeslee, J. R., Olsen, R. G.: Inactivation of tumor cell-associated feline oncornavirus for preparation of an infectious virus-free tumor cell immunogen. Cancer Res. 36, 1647 (1976)
Herberman, R. B., Rosenberg, E. B., Halterman, R. H.: Cellular immune reactions to human leukemia. Natl. Cancer Inst. Monogr. 35, 259 (1972)
Lamon, E. W., Gatti, R. A., Kiessling, R., Fenyo, E. M.: Comparison of the allospecific and viral-specific immune responses to irradiated versus formaldehyde-fixed allogeneic Moloney lymphoma cells in CBA mice. Cancer Res. 35, 962 (1975)
Larson, C. L., Ushyima, R. N., Florey, M. J., Baker, R. E., Baker, M. B.: Effect of BCG on Friend disease virus in mice. Nature New Biol. 229, 240 (1971)
Larson, C. L., Baker, R. E., Ushyima, R. N., Baker, M. B., Gillespie, C.: Immunotherapy of Friend disease in mice employing viable BCG vaccine. Proc. Soc. Exp. Biol. Med. 140, 700 (1972)
Laucius, J. F., Bodurtha, A. J., Mastrangelo, M. J., Creech, H.: Bacillus Calmette-Guérin in the treatment of neoplastic disease. J. Reticuloendothel. Soc. 16, 347 (1974)
Lilly, F.: Antigen expression on spleen cells of Friend virus infected mice. In: RNA Viruses and Host Genomes in Oncogenesis. Emmelot, P., Bentvelzen, P. (eds.), p. 229. Amsterdam: North-Holland 1972
Mackaness, G. B., Lagrange, P. H., Ishibashi, T.: The modifying effect of BCG on the immunological induction of T-cells. J. Exp. Med. 139, 1540 (1974)
Mathé, G., Pouillart, P., Papeyraque, F.: Active immunotherapy of L1210 leukemia applied after the graft of tumor cells. Br. J. Cancer 23, 814 (1969a)
Mathé, G., Amiel, J. L., Schwarzenberg, L., Schneider, M., Cattan, A., Schlumberger, J. R., Hayert, M., De Vassal, F.: Active immunotherapy for acute lymphoblastic leukemia. Lancet 1969 1, 697 (1969b)
Metzgar, R. S., Mohanakumar, T., Bolognesi, D. P.: Relationship between membrane antigens of human leukemic cells and oncogenic RNA virus structural components. J. Exp. Med. 143, 47 (1976)
Miller, T. E., Mackaness, G. B., Lagrange, P. H.: Immunopotentiation with BCG. II. Modulation of the response to sheep red blood cells. J. Natl. Cancer Inst. 51, 1669 (1973)
Oldham, R. K., Weiner, R. S., Mathé, G., Breard, J., Simmler, M. C., Carde, P., Herberman, R. B.: Cell-mediated immune responsiveness of patients with acute lymphocytic leukemia in remission. Int. J. Cancer 17, 326 (1976)
Prowles, R. L., Crowther, D., Bateman, C. J. T., Beard, M. E. J., McElwain, T. J., Russell, J., Lister, T. A., Whittmise, J. M. A., Wrigley, P. F. M., Pike, M., Alexander, P., Hamilton-Fairley, G.: Immunotherapy for acute myelogenous leukemia. Br. J. Cancer 28, 365 (1973)
Rich, M. A., Geldner, J., Meyers, P.: Studies on murine leukemia. J. Natl. Cancer Inst. 35, 523 (1965)
Rich, M. A., Siegler, R., Karl, S., Clymer, R.: Spontaneous regression of virus-induced murine leukemia. I. Host-virus system. J. Natl. Cancer Inst. 42, 559 (1969a)
Rich, M. A., Clymer, R., Karl, S.: Spontaneous regression in virus-induced murine leukemia. II. Influence of environmental factors. J. Natl. Cancer Inst. 42, 571 (1969b)
Rich, M. A., Clymer, R.: Host response in spontaneous regression of murine leukemia. Cancer Res. 31, 803 (1971)
Rich, M. A., Karl, S., Clymer, R.: Complement fixation in conventional and regressing virus-induced murine leukemia. J. Immunol. 106, 1488 (1971)
Russell, J. A., Chapius, B., Powles, P. L.: Various uses of BCG and allogeneic acute leukemia cells to treat patients with acute myelogenous leukemia. Cancer Immunol. Immunother. 1, 87 (1976)
Russo, I., Russo, J., Baldwin, J., Rich, M. A.: Histopathology of spontaneous regression in virus-induced murine leukemia. Am. J. Pathol. 85, 73 (1976)
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Hines, D., Dietz, M., Rich, M.A. et al. Active immunotherapy of friend virus-induced erythroleukemia and its spontaneous regression. Cancer Immunol Immunother 5, 11–16 (1978). https://doi.org/10.1007/BF00199201
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DOI: https://doi.org/10.1007/BF00199201