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Therapeutic application of various immunostimulators on the L2C guinea-pig leukemia

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Summary

Immunostimulators such as Corynebacterium parvum (C. parvum), Bacillus Calmette-Guerin (BCG), pyran copolymer, and glucan were examined in the guinea pig L 2 C lymphoblastic leukemia model to determine their capacity for therapeutic modulation of the immune response of the host toward controlling leukemic cell proliferation. The dose, route, and frequency of administration of the stimulators were also evaluated as a function of time in order to obtain an optimal antileukemic effect. Results indicated that only C. parvum and BCG were capable of significantly increasing host survival when given 1 day after an inoculation of 1.5×104 viable leukemic cells. Administration of BCG or C. parvum, alone or in combination with irradiated blast cells on either days 4 or 7, was totally ineffective in prolonging survival. In the majority of cases, enhanced leukemic growth was observed on these days. The combination of BCG and/or C. parvum with irradiated syngeneic blast cells given 24 h after leukemia inoculation promoted a synergistic response with a significant increase in median survival time and a number of long-term survivors.

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References

  • Alexander, P., Bensted, J., Delorme, E. J., Hall, J. G., Hodgett, J.: The cellular immune response to primary sarcomata in rats. II. Abnormal responses of nodes draining the tumor. Proc. roy. Soc. B 174, 237 (1969)

    Google Scholar 

  • Bansal, S. C., Sjogren, H. O.: Effect of BCG on various facets of the immune response against polyoma tumors in rats. Int. J. Cancer 11, 162 (1973)

    Google Scholar 

  • Barlett, G. L., Zbar, B., Rapp, H. J.: Suppression of murine tumor growth by immune reaction to the Bacillus Calmette Guerin strain of Mycobacterium bovis. J. nat. Cancer Inst. 48, 245 (1972)

    Google Scholar 

  • Bomford, R.: Active specific immunotherapy of mouse methylcholanthrene induced tumors with Corynebacterium parvum and irradiated tumor cells. Brit. J. Cancer 32, 551 (1975)

    Google Scholar 

  • Chirigos, M. A., Pearson, J. W., Pryor, J.: Augmentation of a chemotherapeutically induced remission of a murine leukemia by a chemical immunoadjuvant. Cancer Res. 33, 2615 (1973)

    Google Scholar 

  • Chirigos, M. A., Fuhrman, F., Pryor, J.: Prolongation of chemotherapeutically induced remission of a syngeneic murine leukemia by L-2, 3, 5, 6-Tetrahydro-6-phenylimidazo [2,1-b] thiazole hydrochloride. Cancer Res. 35, 927 (1975)

    Google Scholar 

  • Currie, G. A., Bagshawe, K. D.: Active immunotherapy with Corynebacterium parvum and chemotherapy in murine fibrosarcomas. Brit. med. J. 1970 I, 541

    Google Scholar 

  • Del Guercio, P.: Effect of adjuvants on the antibody response to a hapten on a thymus independent carrier. Nature (Lond.) New Biol. 238, 213 (1972)

    Google Scholar 

  • DiLuzio, N. R.: Macrophages, recognition factors and neoplasia. In: The Reticuloendothelial System (International Academy of Pathology Monograph), Chap. 5, p. 49. Baltimore, Md.: Williams and Wilkins 1975

    Google Scholar 

  • DiLuzio, N. R., Hoffmann, E. O., Cook, J. A., Browder, W., Mansell, P. W. A.: Glucan induced enhancement in host resistance to experimental tumors. In: Control of neoplasia by the modulation of the immune response, Vol. 2, p. 475 (M. A. Chirigos, Ed.). New York: Raven Press 1976

    Google Scholar 

  • Ebbesen, P.: Influence of DEAE-dextran, polybrene, dextran and dextran sulfate on spontaneous leukemia development in AKR mice and virus induced leukemia in BALB/c mice. Brit. J. Cancer 30, 68 (1974)

    Google Scholar 

  • Fidler, I. J., Kataoka, T., Hanna, M. G., Jr.: A comparison of in vitro cell-mediated reactivity against syngeneic tumor cells by various lymphoid cell populations from Bacillus Calmette Guerin tumor-cured, tumor-sensitized, tumor-bearing, and normal inbred guinea pigs. Cancer Res. 36, 4459 (1976)

    Google Scholar 

  • Fisher, B., Wolmark, N., Coyle, J.: Effect of Corynebacterium parvum on cytotoxicity of regional and nonregional lymph node cells from animals with tumors present or removed. J. nat. Cancer Inst. 53, 1793 (1974)

    Google Scholar 

  • Halpern, B., Fray, A., Crepin, Y., Platica, O., Lorinet, A. M., Rabourdin, A., Sparros, L., Isac, R.: Corynebacterium parvum, a potent immunostimulant in experimental infections and in malignancies. In: Immunopotentiation. Ciba Foundation Symposia, no. 18, p. 217 (J. Knight, Ed.). Amsterdam: Associated Scientific Publishers 1973

    Google Scholar 

  • Howard, J. G., Scott, M. T., Christie, G. H.: Cellular mechanisms underlying the adjuvant activity of Corynebacterium parvum: interactions of activated macrophages with T and B lymphocytes. In: Immunopotentiators. Ciba Foundation Symposia, no. 18, p. 101 (J. Knight, Ed.). Amsterdam: Associated Scientific Publishers 1973

    Google Scholar 

  • Klein, D. L., Pearson, J. W.: Modulation of host immune response against the L2C guinea pig leukemia. Fed. Proc. 36, 2276 (1977)

    Google Scholar 

  • Likhite, V. V., Halpern, B. N.: The delayed rejection of tumors formed from the administration of tumor cells mixed with killed Corynebacterium parvum. Int. J. Cancer 12, 699 (1973)

    Google Scholar 

  • Likhite, V. V., Halpern, B. N.: Lasting rejection of mammary adenocarcinoma cell tumors in DBA/2 mice with intratumor injection of killed Corynebacterium parvum. Cancer Res. 34, 341 (1974)

    CAS  PubMed  Google Scholar 

  • Littman, B. H., Meltzer, M. S., Cleveland, R. P., Zbar, B., Rapp, H. J.: Tumor-specific cell-mediated immunity in guinea pigs with tumors. J. nat. Cancer Inst. 51, 1627 (1973)

    Google Scholar 

  • Mathé, G.: Cancer active immunotherapy, immunoprophylaxis and immunorestoration: an introduction. In: Recent Results in Cancer Research, Vol. 55, p. 76 (G. Mathé, Ed.). Berlin-New York-Heidelberg: Springer 1976

    Google Scholar 

  • Mathé, G., Amiel, J. L., Schwarzenberg, L., Schneider, M., Catton, A., Schlumberger, J. R., Hayat, M., DeVassol, F.: Active immunotherapy for acute lymphoblastic leukemia. Lancet 1969a I, 697

    Google Scholar 

  • Mathé, G., Pouillart, P., Lapeyraque, F.: Active immunotherapy of L1210 leukemia applied after the graft of tumor cells. Brit. J. Cancer 23, 814 (1969b)

    Google Scholar 

  • Mathé, G., Kamel, M., Dezfulian, J., Halle-Pannenko, O., Bourut, C.: An experimental screening for “systemic adjuvants of immunity” applicable in cancer immunotherapy. Cancer Res. 33, 1987 (1973a)

    Google Scholar 

  • Mathé, G., Halle-Pannenko, O., Bourut, C.: Active immunotherapy in spontaneous leukemia of AKR mice. Exp. Hemat. 1, 110 (1973b)

    Google Scholar 

  • Mathé, G., Halle-Pannenko, O., Bourut, C.: Immune manipulation by BCG administered before or after cyclophosphamide for chemo-immunotherapy of L1210 leukemia. Europ. J. Cancer 10, 661 (1974)

    Google Scholar 

  • Milas, L.: Tumor immunotherapy with anaerobic corynebacteria: Assessment with lung colony assay. In: Immunopotentiation. Ciba Foundation Symposia, no. 18, p. 217 (J. Knight, Ed.). Amsterdam: Associated Scientific Publishers 1973

    Google Scholar 

  • Milas, L., Gutterman, J. V., Basić, I., Hunter, N., Mavligit, G. M., Hersh, E. M., Withers, H. R.: Immunoprophylaxis and immunotherapy for a murine fibrosarcoma with C. granulosum and C. parvum. Int. J. Cancer 14, 493 (1974)

    CAS  PubMed  Google Scholar 

  • Mohr, S. J., Chirigos, M. A., Fuhrman, F. S., Pryor, J. W.: Pyran copolymer as an effective adjuvant to chemotherapy against a murine leukemia and solid tumor. Cancer Res. 35, 3750 (1975)

    Google Scholar 

  • Mohr, S. J., Chirigos, M. A., Smith, G. T., Fuhrman, F. S.: Specific potentiation of L1210 vaccine by pyran copolymer. Cancer Res. 36, 2035 (1976)

    Google Scholar 

  • Morahan, P. S., Munson, J. A., Baird, L. G., Kaplan, A. M., Regelson, W.: Antitumor action of pyran copolymer and tilorone against Lewis lung carcinoma and B16 melonoma. Cancer Res. 34, 506 (1974)

    Google Scholar 

  • Parr, I.: Response of syngeneic murine lymphomata to immunotherapy in relation to the antigenicity of the tumor. Brit. J. Cancer 26, 174 (1972)

    Google Scholar 

  • Pearson, J. W., Pearson, G. R., Gibson, W. T., Chermann, J. C., Chirigos, M. A.: Combined chemoimmunostimulation therapy against murine leukemia. Cancer Res. 32, 904 (1972)

    CAS  PubMed  Google Scholar 

  • Pearson, J. W., Chaparas, S. D., Chirigos, M. A.: Effect of dose and route of Bacillus Calmette-Guérin in chemoimmunostimulation therapy of a murine leukemia. Cancer Res. 33, 1845 (1973)

    Google Scholar 

  • Pearson, J. W., Chirigos, M. A., Chaparas, S. D., Sher, N. A.: Combined drug and immunostimulation therapy against a syngeneic murine leukemia. J. nat. Cancer Inst. 52, 463 (1974)

    Google Scholar 

  • Pendergrast, W. J., Jr., Drake, W. P., Mardiney, M. R., Jr.: The dependence of successful immunotherapy on adequate tumor burden as shown by the treatment of AKR leukemia with poly A. poly V. J. nat. Cancer Inst. 55, 1223 (1975)

    Google Scholar 

  • Perk, K., Pearson, J. W., Torgersen, J. A., Chirigos, M. A.: An animal model for meningeal leukemia. Int. J. Cancer 13, 863 (1974)

    Google Scholar 

  • Powles, R. L., Balchin, L. A., Hamilton-Fairley, G.: Recognition of leukemia cells as foreign before and after autoimmunization. Brit. Med. J. 1971 I, 486

    Google Scholar 

  • Proctor, J., Rudenstam, C. M., Alexander, P.: Increased incidence of lung metastase following treatment of rats bearing hepatomas with irradiated tumor cells and the beneficial effect of Corynebacterium parvum in this system. Biomedicine 19, 248 (1973)

    Google Scholar 

  • Sampson, D., Peters, T. G., Lewis, J. D., Metzig, J., Kortz, B. E.: Dose dependence of immunopotentiation and tumor regression induced by Levamisole. Cancer Res. 37, 3526 (1977)

    Google Scholar 

  • Schlossman, S. F., Chess, L., Humphreys, R. E., Strominger, J. L.: Distribution of Ia-like molecules on the surface of normal and leukemic human cells. Proc. nat. Acad. Sci. (Wash.) 73, 1288 (1976)

    Google Scholar 

  • Scott, M. T.: Corynebacterium parvum as a therapeutic antitumor agent in mice. II. Local injection. J. nat. Cancer Inst. 53, 861 (1974)

    Google Scholar 

  • Scott, M. T.: Potentiation of the tumor-specific immune response by Corynebacterium parvum. J. nat. Cancer Inst. 55, 65 (1975)

    Google Scholar 

  • Scott, M. T., Bomford, R.: Comparison of the potentiation of specific tumor immunity in mice by Corynebacterium parvum or BCG. J. nat. Cancer Inst. 57, 555 (1976)

    Google Scholar 

  • Shevach, E. M., Ellman, L., Davie, J. M., Green, I.: L2C guinea pig lymphatic leukemia: A “B” cell leukemia. Blood 39, 1 (1972)

    Google Scholar 

  • Smith, S. E., Scott, M. T.: Biological effects of Corynebacterium parvum: II Amplification of resistance and impairment of active immunity to murine tumors. Brit. J. Cancer 26, 361 (1972)

    CAS  PubMed  Google Scholar 

  • Woodruff, M. F. A., Boak, J. L.: Inhibitory effect of injections of Corynebacterium parvum on the growth of tumor transplants in isogenic hosts. Brit. J. Cancer 20, 345 (1966)

    Google Scholar 

  • Woodruff, M. F. A., Ghaffar, A., Dunbar, N., Whitehead, V. L.: Effect of C. parvum on immunization with irradiated tumor cells. Brit. J. Cancer 33, 491 (1976)

    Google Scholar 

  • Zbar, B., Berstein, I. D., Rapp, H. J.: Suppression of tumor growth at the site of infection with living Bacillus Calmette-Guerin. J. nat. Cancer Inst. 46, 831 (1971)

    Google Scholar 

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Authors and Affiliations

  1. Viral Immunotherapy Section, Laboratory of RNA Tumor Viruses, National Cancer Institute, National Institutes of Health, 20014, Bethesda, Maryland, USA

    D. L. Klein, W. Brown & J. W. Pearson

  2. Flow Laboratory, Inc., 1710 Chapman Avenue, 20852, Rockville, Maryland, USA

    P. Cote & W. Garner

Authors
  1. D. L. Klein
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  2. W. Brown
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  3. P. Cote
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  4. W. Garner
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  5. J. W. Pearson
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This work was supported by contract N01-CP-53566 within the Virus Cancer Program of the National Cancer Institute

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Klein, D.L., Brown, W., Cote, P. et al. Therapeutic application of various immunostimulators on the L2C guinea-pig leukemia. Cancer Immunol Immunother 4, 229–237 (1978). https://doi.org/10.1007/BF00200153

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  • DOI: https://doi.org/10.1007/BF00200153

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