DIRECT AND INDIRECT EFFECTS OF HUMAN RECOMBINANT GAMMA-INTERFERON ON TUMOR-CELLS IN A CLONOGENIC-ASSAY

  • 1 March 1986
    • journal article
    • research article
    • Vol. 46  (3) , 1142-1147
Abstract
Purified, recombinant human .gamma.-interferon (rIFN-.gamma.) was tested at clinically achievable doses for direct and indirect antiproliferative activity against human tumor cell lines using a clonogenic assay. One-h treatment with rIFN-.gamma. showed direct dose dependent inhibition of tumor colony growth in cell lines established from human melanoma, myeloma, renal cell, and cervical cancers. Longer treatments resulted in suppression of ovarian and breast carcinoma clonogenicity. In order to test for indirect antiproliferative effects of rIFN-.gamma., feeder cells were included in a separate agarose underlayer in the cloning assay. These feeder cells included mouse peritoneal macrophage, U-937 (human histiocytic lymphoma cell line), and adherent cells from human malignant ascites specimens. Colony growth of ovarian carcinoma and melanoma cell lines was stimulated by each of these feeder cell types. Cultures containing mouse peritoneal macrophages or U-937 cells showed the same antiproliferative responses to rIFN-.gamma. as did control cultures without feeder cells. In contrast, human adherent ascites cells (> 80% macrophages) became strongly inhibitory to tumor colony growth when treated with rIFN-.gamma.. These results suggest that human tumor associated macrophages may become tumoricidal under the influence of rIFN-.gamma., producing a diffusable substances in agarose culture which causes the observed antiproliferative effects on tumor cells.