Effects of leukocyte interferon (E. coli) on human bone sarcoma growth in vitro and in the nude mouse

Effects of highly purified human leukocyte interferon (rIFN-alpha 2) on colony formation, DNA synthesis and proliferation in nude mice of tumor cells from eight bone sarcomas have been studied. rIFN-alpha 2 produced a dose-dependent inhibition of [3H]thymidine incorporation by sarcoma cells. Even at high doses (10(4) U/ml), however, [3H]thymidine uptake could not be completely blocked by rIFN-alpha 2. In a cloning assay three established sarcoma cell lines and five other sarcoma samples obtained after short-term in vitro culture were found to be sensitive to various degrees to rIFN-alpha 2, complete inhibition being seen only at 10(4) U/ml. Three sarcomas were sensitive in the nude mouse model. Scheduling experiments revealed that rIFN-alpha 2 produces a delay in tumor growth only when administered either before or shortly after tumor implantation. Therefore rIFN-alpha 2 appears to be most active when tumor size is small and growth not exponential, indicating that rIFN-alpha 2 may play a role in an adjuvant setting. Growth sarcomas strongly suppressed by rIFN-alpha 2 in the cloning assay was markedly inhibited in the nude mouse. One sarcoma which was only moderately sensitive in the cloning assay was resistant in the animal experiment, confirming the predictive value of the clonogenic assay. Although the present findings demonstrate strong antitumor activity of rIFN-alpha 2 against human bone sarcoma cells they should be interpreted with caution mainly because the high rIFN-alpha 2 levels used in the experiments cannot be maintained in patients over a prolonged period.