Antiproliferative activity of human interferons against ovarian cancer cells grown in human tumor stem cell assay.

Fresh biopsies from 14 of 22 (64%) ovarian carcinomas cultivated in the human tumor stem cell assay (HTSCA) were sensitive (greater than 70% inhibition in cell growth) to human interferons (HuIFNs). To achieve 70% inhibition of colony growth, 500 units/ml of a naturally produced IFN-alpha or IFN-alpha A were required in 71% of the sensitive specimens. The antiproliferative potencies of five IFNs were evaluated including two native alpha IFNs, two highly purified cloned subtypes of IFN-alpha, IFN-alpha D and IFN-alpha A, and one native fibroblast-derived beta interferon (IFN-beta). The antiviral activity of the IFN-alpha as determined by a human cell target correlated with their relative antiproliferative action. IFN-alpha D had minimal inhibitory effect at the highest concentration tested, while three IFN-alpha 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-beta had significantly less growth inhibitory potency for cells from ovarian cancers when compared simultaneously with native IFN-alpha in the human tumor stem cell assay (HTSCA). Assuming direct antiproliferative effects are primary, future clinical trials evaluating IFN-alpha in ovarian cancer may require high titers of IFN.