Increased immunogenicity of surviving tumor cells enables cooperation between liposomal doxorubicin and IL-18.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BioMed Central, 2003-
    • Subject Terms:
      Antibiotics, Antineoplastic*/immunology ; Antibiotics, Antineoplastic*/therapeutic use ; Doxorubicin*/immunology ; Doxorubicin*/therapeutic use ; Interleukin-18*/immunology ; Interleukin-18*/therapeutic use; Ovarian Neoplasms/*drug therapy ; Ovarian Neoplasms/*immunology; Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Female ; Humans ; Immunophenotyping ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Ovarian Neoplasms/pathology ; Survival Rate
    • Abstract:
      Background: Liposomal doxorubicin (Doxil) is a cytotoxic chemotherapy drug with a favorable hematologic toxicity profile. Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated.
      Methods: Using ID8 murine ovarian cancer cells, the immunomodulatory effects of Doxil were studied by measuring its impact on ovarian cancer cell expression of MHC class-I and Fas, and susceptibility to immune attack in vitro. To evaluate the ability of Doxil to cooperate with cancer immunotherapy, the interaction between Doxil and Interleukin 18 (IL-18), a pleiotropic immunostimulatory cytokine, was investigated in vivo in mice bearing ID8-Vegf tumors.
      Results: While Doxil killed ID8 tumor cells in a dose-dependent manner, tumor cells escaping Doxil-induced apoptosis upregulated surface expression of MHC-I and Fas, and were sensitized to CTL killing and Fas-mediated death in vitro. We therefore tested the hypothesis that the combination of immunotherapy with Doxil provides positive interactions. Combination IL-18 and Doxil significantly suppressed tumor growth compared with either monotherapy in vivo and uniquely resulted in complete tumor regression and long term antitumor protection in a significant proportion of mice.
      Conclusion: These data demonstrate that Doxil favorably changes the immunophenotype of a large fraction of the tumor that escapes direct killing thus creating an opportunity to expand tumor killing by immunotherapy, which can be capitalized through addition of IL-18 in vivo.
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    • Grant Information:
      R01 CA105216 United States CA NCI NIH HHS; R01 CA105216-05 United States CA NCI NIH HHS
    • Accession Number:
      0 (Antibiotics, Antineoplastic)
      0 (Interleukin-18)
      80168379AG (Doxorubicin)
    • Publication Date:
      Date Created: 20091217 Date Completed: 20100125 Latest Revision: 20211020
    • Publication Date:
      20240829
    • Accession Number:
      PMC2797002
    • Accession Number:
      10.1186/1479-5876-7-104
    • Accession Number:
      20003308