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. 1987 Feb;24(1):64–67. doi: 10.1007/BF00199834

Adoptive immunity in mice challenged with L1210/DTIC clones

Gianfranco Canti 1,, Laura Ricci 1, Ornella Marelli 1, Paola Franco 1, Angelo Nicolin 2
PMCID: PMC11038223  PMID: 3545466

Abstract

New antigenic specificities, not detectable on parental cells, have been induced by many investigators in mouse lymphomas by treatment with the antitumor agent 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The antigens are transmissible, after withdrawal of the drug treatment, as an inheritable character. The mechanism of induction, the molecular nature, and the number of the new antigenic specificities have not been completely elucidated. Four clones from murine leukemia L1210 isolated and expanded in vitro were treated in vivo with DTIC and the new sublines were studied in detail. The four drug-treated sublines studied exhibited strong immunogenicity since they were rejected by syngeneic animals. Immunosuppressed animals challenged with 107 A/DTIC or P/DTIC cells were reciprocally protected by the adoptive transfer of spleen cells from donors that had rejected a lethal challenge of A/DTIC or P/DTIC clones. In a similar fashion, the adoptive transfer of spleen cells obtained from animals that had rejected the Q/DTIC or the R/DTIC clones protected immunosuppressed mice challenged with Q/DTIC or R/DTIC cells. No antitumor activity was observed in cross-protective schedules other than those indicated. It was been concluded that (a) the L1210 leukemia line does not have antigenic cells, (b) four DTIC-treated clone sublines were rejected by compatible hosts, and (c) two mutually exclusive sets of antigens were expressed in four antigenic clone sublines.

Keywords: Leukemia, Spleen Cell, Antigenic Specificity, Adoptive Transfer, Antitumor Agent

Footnotes

Research supported in part by P.F.O. Contract Grant from C. N. R., Rome, Italy

References

  • 1.Bonmassar E, Bonmassar A, Vladamudi S, Goldin A. Immunological alteration of leukemic cells “in vivo” after treatment with an antitumor drug. Proc Natl Acad Sci. 1970;66:1089. doi: 10.1073/pnas.66.4.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Bonmassar E, Bonmassar A, Vladamudi S, Goldin A. Antigenic changes of L1210 leukemia in mice treated with 5-(3,3-dimethyl-1-triazeno-4-carboxamide. Cancer Res. 1972;32:1446. [PubMed] [Google Scholar]
  • 3.Bonmassar E, Nicolin A, Spreafico F. Drug-induced modifications of tumor cell antigenicity. Tumor-associated antigens and their specific immune response. Proceed Serono Symposia. 1979;16:260. [Google Scholar]
  • 4.Boon T. Antigenic tumor cell variants obtained with mutagens. Adv Cancer Res. 1983;39:121. doi: 10.1016/s0065-230x(08)61034-9. [DOI] [PubMed] [Google Scholar]
  • 5.Calman NS, Eng B, Slater LM, Wallerstein H. Antigenic changes associated with resistance to methotrexate and 6-mercaptopurine in L1210 ascites lymphoma. J Natl Cancer Inst. 1974;52:997. doi: 10.1093/jnci/52.3.997. [DOI] [PubMed] [Google Scholar]
  • 6.Fuji H, Bernacki R, Mihich E. Increased immunogenicity and antigenicity of L1210 lymphomas resistant to antileukemic agents as measured in vitro. Fed Proc. 1974;33:781. [Google Scholar]
  • 7.Giampietri A, Fioretti MC, Goldin A, Bonmassar E. Drug mediated antigenic changes in murine leukemia cells: Antagonistic effect of quinacrine in antimutagenic compounds. J Natl Cancer Inst. 1980;64:297. doi: 10.1093/jnci/64.2.297. [DOI] [PubMed] [Google Scholar]
  • 8.Kitano M, Mihich E, Pressman D. Antigenic differences between leukemia L1210 and a subline resistant to methylglyoxal-bis (guanylhydrazone) Cancer Res. 1972;32:181. [PubMed] [Google Scholar]
  • 9.Marelli O, Mantovani A, Franco P, Nicolin A. Macrophage antitumor activity induced by the antigenic lymphoma L5178Y/DTIC subline. Tumori. 1982;68:365. doi: 10.1177/030089168206800502. [DOI] [PubMed] [Google Scholar]
  • 10.Marelli O, Canti G, Franco P, Prandoni M, Ricci L, Nicolin A L1210/DTIC antigenic subline: studies at the clone level. Eur J Cancer (in press) [DOI] [PubMed]
  • 11.Mihich E. Modfication of tumor regression by immunological means. Cancer Res. 1969;29:3345. [PubMed] [Google Scholar]
  • 12.Nicolin A, Bini A, Coronetti E, Goldin A. Cellular immunoresponse to a drug-treated L5178Y lymphoma subline. Nature. 1974;251:654. doi: 10.1038/251654a0. [DOI] [PubMed] [Google Scholar]
  • 13.Nicolin A, Canti G, Goldin A. Adoptive immunotherapy in Balb/c × DBA/2CF1 mice bearing an immunogenic subline of L1210 leukemia. Cancer Res. 1974;34:3044. [PubMed] [Google Scholar]
  • 14.Nicolin A, Spreafico F, Bonmassar E, Goldin A. Antigenic changes of L5178Y lymphoma after treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide in vivo. J Natl Cancer Inst. 1976;56:89. doi: 10.1093/jnci/56.1.89. [DOI] [PubMed] [Google Scholar]
  • 15.Nicolin A, Franco P, Testorelli C, Goldin AM. Immunosensitivity and histocompatibility antigens in drug-altered leukemic cells. Cancer Res. 1976;36:222. [PubMed] [Google Scholar]
  • 16.Nicolin A, Canti G, Marelli O, Veronese F, Goldin A. Chemotherapy and immunotherapy of L1210 leukemic mice with antigenic tumor sublines. Cancer Res. 1981;41:1358. [PubMed] [Google Scholar]
  • 17.Schmid FA, Hutchinson DJ. Decrease in oncogenic potential of L1210 leukemia by triazenes. Cancer Res. 1973;33:2161. [PubMed] [Google Scholar]
  • 18.Schmid FA, Hutchinson DJ. Decrease in oncogenic potential of L1210 leukemia by triazenes. Cancer Res. 1973;33:2161. [PubMed] [Google Scholar]
  • 19.Silvestrini R, Testorelli C, Goldin A, Nicolin A. Cell kinetics and immunogenicity of lymphoma cells treated with (+(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) in vivo. Int J Cancer. 1977;19:664. doi: 10.1002/ijc.2910190510. [DOI] [PubMed] [Google Scholar]
  • 20.Spreafico F, Mantovani A, Menconi E. Immunosuppressive activity of dimethyl-triazeno-imidazole-carboxamide (DTIC) in mice. Fed Proc. 1974;33:572. [Google Scholar]
  • 21.Testorelli C, Franco P, Goldin A, Nicolin A. In vitro lymphocyte stimulation and the generation of cytotoxic lymphocytes with drug-induced antigenic lymphomas. Cancer Res. 1978;38:830. [PubMed] [Google Scholar]

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