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Inhibition of a mouse hepatoma by the alkylating agent trenimon linked to immunoglobulins

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Summary

Trenimon was conjugated in active alkylating form to rabbit anti-mouse H6 hepatoma globulin (AHG) with retention of antibody activity. H6 hepatoma-inoculated mice were given various combinations of conjugates, free Trenimon, and unconjugated immunoglobulins in daily injections for 5 days. Linkage of Trenimon to immunoglobulins reduced systemic toxicity of the drug, with comparative retention of its antitumor activity. The antitumor action of Trenimon was potentiated by AHG irrespective of whether the drug was directly linked to AHG or free AHG was administered along with Trenimon linked to normal rabbit globulin (NRG).

In vitro, Trenimon bound to AHG was less inhibitory to hepatoma cells than free Trenimon, but more inhibitory than Trenimon-NRG conjugates. There was no significant endocytosis of conjugates by the hepatoma cells. This suggests that unlike free Trenimon, the target molecules of Trenimon-immunoglobulin conjugates are not intracellular DNA but are located on the surface of the hepatoma cells.

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Authors and Affiliations

  1. Department of Pathology, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada

    Tarun Ghose & Alev Guclu

  2. Department of Microbiology, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada

    Tarun Ghose & R. Raja Raman

  3. Department of Biochemistry, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada

    A. Huntley Blair

Authors
  1. Tarun Ghose
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  2. Alev Guclu
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  3. R. Raja Raman
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  4. A. Huntley Blair
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Ghose, T., Guclu, A., Raman, R.R. et al. Inhibition of a mouse hepatoma by the alkylating agent trenimon linked to immunoglobulins. Cancer Immunol Immunother 13, 185–189 (1982). https://doi.org/10.1007/BF00205386

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  • DOI: https://doi.org/10.1007/BF00205386

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