GUINEA-PIG LINE 10 HEPATO-CARCINOMA MODEL - CHARACTERIZATION OF MONOCLONAL-ANTIBODY AND INVIVO EFFECT OF UNCONJUGATED ANTIBODY AND ANTIBODY CONJUGATED TO DIPHTHERIA TOXIN-A CHAIN

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (9) , 4420-4428
Abstract
Monoclonal antibodies were raised against the guinea pig line 10 (L10) hepatocarcinoma, and an IgG1-producing hybridoma (D3) was selected for further study. D3 is a true monoclonal antibody as demonstrated by 2-dimensional gel electrophoresis. Radioimmunoassays on live cells revealed no cross-reactivity with normal tissues or with the line 1 hepatocarcinoma which was used as a control. Membrane immunofluorescence assays demonstrated similar specificity. Immunoperoxidase staining of cryostat sections of tumor and normal tissues of both adult animals and fetuses showed that the D3 monoclonal antibody reacted primarily with the L10 tumor, but some cross-reactivity with smooth muscle, placenta, fetal skeletal muscle, and fetal liver was also demonstrated. Radioimmunoprecipitation of detergent extracts of iodinated L10 cells showed that the antigen is present on the cell surface as a dimer of MW 290,000 (unit size, MW 148,000). Therapy studies with unconjugated D3 antibody demonstated a minor dose-dependent effect on tumor growth. D3 antibody conjugated to the A chain of diphtheria toxin (10-7 M) was cytotoxic to 100% of L10 cells in vitro. Animals treated with a single 1-mg i.v. injection of this immunoconjugate on day 7 following the intradermal injection of 105 tumor cells demonstrated a highly significant inhibition of tumor growth compared to control animals and those treated with unconjugated antibody.

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