Role of host defense mechanisms in the antitumor activity of adriamycin and daunomycin in mice

A. Mantovani, N. Polentarutti, W. Luini, G. Peri, F. Spreafico

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The role of host defense mechanisms in the anti-neoplastic activity of the two analogs adriamycin (AM) and daunomycin (DM) was investigated in (BALB/c x DBA/2)F 1 mice inoculated with the nonimmunogenic L1210 Cr leukemia, the immunogenic SL2 lymphoma, and the strongly immunogenic L1210 Ha leukemia. The higher the immunogenicity of the tumor, the greater was the therapeutic efficacy of AM. Prior treatment with the immunosuppressant 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) markedly impaired the efficacy of AM in immunogenic tumor models, and similarly, the antitumor activity of AM was decreased in thymus-deprived mice. Suppression of host defense mechanisms by DTIC as late as 9 days after chemotherapy was still effective in reducing the number of mice eventually cured by AM in the DTIC-resistant L1210 Ha leukemia system. This suggested that viable L1210 Ha leukemia cells persisted for at least 9 days after optimal AM chemotherapy and that their growth was inhibited by host immune responses. The antitumor activity of DM was not significantly affected by tumor immunogenicity and host immunologic status. Macrophages obtained from L1210 Ha leukemia-inoculated, AM-cured mice were activated and nonspecifically inhibited growth and DNA synthesis of tumor cells in vitro. The antimacrophage agents silica and carrageenan significantly reduced the efficacy of AM in immunogenic tumor models but had no effect on DM. Conversely, combinations of AM with the macrophage activator Corynebacterium parvum showed a significant therapeutic synergism, whereas chemoimmunotherapy with DM was not more active than chemotherapy alone. Results from these experiments were consistent with the hypothesis that host defense mechanisms play a role in the stronger antitumor activity of AM compared to its analog DM and suggest that macrophages contribute to the therapeutic efficacy of AM.

Original languageEnglish
Pages (from-to)61-66
Number of pages6
JournalJournal of the National Cancer Institute
Issue number1
Publication statusPublished - 1979

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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