Summary
The effectiveness of neuraminidase-treated, drug-resistant L1210 sublines in active immunotherapy of L1210 leukemia was evaluated. Optimal conditions for the establishment of in vitro, drug-resistant cells included (a) proper drug concentration, (b) the use of logarithmic-phase cultures in fresh medium, containing 5 or 10% serum, and (c) continual exposure to drug. Active immunotherapy, after tumor burden was reduced with chemotherapy, with neuraminidase-treated cells alone was either effective or deleterious, depending upon the drug-resistant subline used for immunization. The combination of BCG and neuraminidase-treated cells was superior to treatment with chemotherapy only. Optimal response was observed with the use of parental L1210 cells, combined with BCG, in immunotherapy of parental L1210 tumor. The results emphasize that an important prerequisite to successful immunotherapy is that tumor vaccines must elicit immunologic products which are cytotoxic for residual tumor.
Similar content being viewed by others
References
Bagshawe, K. D., Currie, G. A.: Immunogenicity of L1210 Murine Leukemia Cells after Treatment with Neuraminidase. Nature 218, 1254 (1968)
Bekesi, J. G., Holland, J. F.: Combined Chemotherapy and Immunotherapy of Transplantable and Spontaneous Murine Leukemia in DBA/2 and AKR Mice. In: Recent Results in Cancer Research, Investigation and Stimulation of Immunity in Cancer Patients. p. 357. New York: Springer 1974
Bekesi, J. G., St. Arneault, G., Holland, J. F.: Increase of Leukemia L1210 Immunogenicity by Vibrio cholerae Neuraminidase Treatment. Cancer Res. 31, 2130 (1971)
Bekesi, J. G., St. Arneault, G., Walter, L., Holland, J. F.: Immunogenicity of Leukemia L1210 Cells after Neuraminidase Treatment. J. Nat. Cancer Inst. 49, 107 (1972)
Brockman, R. W.: Mechanism of resistance to anticancer agents. Advanc. Cancer Res. 7, 129 (1963)
Calman, N. S., Eng, B., Slater, L. M., Wallerstein, H.: Brief communication: Antigenic Changes Associated with Resistance to Methotrexate and 6-mercaptopurine in L1210 Ascites Lymphoma. J. Nat. Cancer Inst. 52, 997 (1974)
Currie, G. A., Bagshawe, K. D.: The Role of Sialic Acid in Antigenic Expression: Further Studies of the Landschutz Ascites Tumor. Brit. J. Cancer 22, 843 (1968)
Currie, G. A., Bagshawe, K. D.: Tumor Specific Immunogenicity of Methylcholanthrene-Induced Sarcoma Cells after Incubation in Neuraminidase. Brit. J. Cancer 23, 141 (1969)
Fischer, G. A.: Nutritional and Amethopterin-resistant Characteristics of Leukemic Clones. Cancer Res. 19, 372 (1959)
Fuji, H., Mihich, E.: Selection for High Immunogenicity in Drug-Resistant Sublines of Murine Lymphomas Demonstrated by Plaque Assay. Cancer Res. 35, 946 (1975)
Hersh, E. M., Gutterman, J. U., Mayligit, G.: Immunotherapy of Cancer in Man. Springfield, Ill.: Charles C. Thomas 1973
Holland, J. F.: E. Pluribus Unum: Presidential Address. Cancer Res. 31, 1319 (1971)
Kessel, D., Bosmann, H. B.: On the characteristics of Actinomycin D Resistance in L5178Y Cells. Cancer Res. 30, 2695 (1970)
Kitano, M., Mihich, E., Pressman, D.: Antigenic Differences Between Leukemia L1210 and a Subline Resistant to Methylglyoxalbis-(guanylhydrazone). Cancer Res. 32, 181 (1972)
Killion, J. J., Kollmorgen, G. M.: Isolation of Immunogenic Tumor Cells by Cell-Affinity Chromatography. Nature 259, 674 (1976)
Klein, G.: Tumor Antigens. Ann. Rev. Microbiol. 20, 674 (1976)
Kollmorgen, G. M., Erwin, D. N., Killion, J. J., Sansing, W. A.: Potential Role of Immunotherapy in Tumor Treatment. Ann. Okla. Acad. Sci. 3, 25 (1973)
Kollmorgen, G. M., Killion, J. J., Sansing, W. A., Cantrell, J. L., Bundren, J. C., LeFever, A. V.: Immunotherapy with Neuraminidase-Treated Cells and BCG. Surgery 79, 202 (1976)
Kollmorgen, G. M., Sansing, W. A., Cantrell, J. L., Killion, J. J., Bundren, J. C.: Combination Chemotherapy-Immunotherapy of Murine Lymphocytic Leukemia. In: Neoplasm Immunity: Theory and Application. p. 27. Chicago: ITR Press 1975
Kollmorgen, G. M., Sansing, W. A., Cox, D., Killion, J. J., Cantrell, J. L.: Induction of Immunity with Immunotherapy. In: Neoplasm Immunity: Mechanisms. Chicago: ITR Press 1976 (In press)
Law, L. W.: Observations on Properties of Leukemic Cells Resistant to Folic Acid Antagonists. J. Nat. Cancer Inst. 11, 849 (1951)
LeFever, A. V., Killion, J. J., Kollmorgen, G. M., Cantrell, J. L.: Immunotherapeutic Value of Neuraminidase-treated, Drug-resistant Tumor Cells. In vitro 10, 388a (1974)
Mihich, E.: In: Cancer and Transplantation, Immunosuppression in Cancer Therapeutics. p. 137. New York: Grune and Stratton 1975
Mihich, E., Kitano, M.: Differences in the Immunogenicity of Leukemia L1210 Sublines in DBA/2 Mice. Cancer Res. 31, 1999 (1971)
Nicolin, A., Vadlamudi, S., Goldin, A.: Antigenicity of L1210 Leukemic Sublines Induced by Drugs. Cancer Res. 32, 653 (1972)
Old, L. J., Boyse, E. A.: Immunology of Experimental Tumors. Ann. Rev. Med. 15, 167 (1964)
Rios, A., Simmons, R. L.: Active, Specific Immunotherapy of Minimal Residual Tumor: Excision Plus Neuraminidase-Treated Tumor Cells. Int. J. Cancer 13, 71 (1974)
Sanford, B. H.: An Alteration in Tumor Histocompatability Induced by Neuraminidase. Transplantation 5, 1273 (1967)
Sansing, W. A., Kollmorgen, G. M.: Humoral Response to Neuraminidase-Treated Tumor Cells. J. Nat. Cancer Inst. (In press)
Sharp, J. D., Capecchi, N. E., Capecchi, M. R.: Altered Enzymes in Drug-resistant Variants of Mammalian Tissue Culture Cells. Proc. Nat. Acad. Sci. 70, 3145 (1973)
Simmons, R. L., Rios, A.: Comparative and Combined Effect of BCG and Neuraminidase in Experimental Immunotherapy. Nat. Cancer Inst. Monogr. 39, 57 (1973)
Simmons, R. L., Rios, A.: Immunospecific Regression of Methylcholanthrene Fibrosarcoma with the Use of Neuraminidase. II. Intratumor Injections of Neuraminidase. Surgery 71, 556 (1972)
Simmons, R. L., Rios, A., Lundgren, G., Ray, P. K., McKhann, C. F., Haywood, G. R.: Immunospecific Regression of Methylcholanthrene Fibrosarcoma with the Use of Neuraminidase. Surgery 70, 38 (1971)
Song, C. W., So, S. K., Simmons, R. L., Levitt, S. H.: Radiotherapy and Immunotherapy of Fibrosarcoma of C3H Mice. Rad. Research 59, 168 (1974)
Author information
Authors and Affiliations
Additional information
Submitted in partial fulfillment of the requirements for the Masters of Science Degree, University of Oklahoma
Rights and permissions
About this article
Cite this article
LeFever, A.V., Killion, J.J. & Kollmorgen, G.M. Active immunotherapy of L1210 leukemia with neuraminidase-treated, drug-resistant L1210 sublines. Cancer Immunol Immunother 1, 211–217 (1976). https://doi.org/10.1007/BF00200095
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00200095