Antiproliferative Activity of Human Interferons Against Ovarian Cancer Cells Grown in Human Tumor Stem Cell Assay

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Abstract
Fresh biopsies from 14 of 22 (64%) ovarian carcinomas cultivated in the human tumor stem cell assay (HTSCA) were sensitive (>70% inhibition in cell growth) to human interferons (HuIFNs). To achieve 10 % inhibition of colony growth, 500 units/ml of a naturally produced IFN-α or IFN-αA were required in 71% of the sensitive specimens. The antiproliferative potencies of five IFNs were evaluated including two native α IFNs, two highly purified cloned subtypes of IFN-α, IFN-αD and IFN-αA, and one native fibroblast-derived beta interferon (IFN-β). The antiviral activity of the IFN-α as determined by a human cell target correlated with their relative antiproliferative action. IFN-αD had minimal inhibitory effect at the highest concentration tested, while three IFN-α with high antiviral activities were equivalent with respect to growth inhibition in the HTSCA. Although instability could not be eliminated as a contributing factor, IFN-β had significantly less growth inhibitory potency for cells from ovarian cancers when compared simultaneously with native IFN-α in the human tumor stem cell assay (HTSCA). Assuming direct antiproliferative effects are primary, future clinical trials evaluating IFN-α in ovarian cancer may require high titers of IFN.