Time-Dependent Cytotoxic Action of Human Recombinant {alpha}-Interferon (Ro22-8181) In Vitro and the Sensitivity of Various Cultured Leukemia and Lymphoma Cell Lines to It

The growth inhibitory activity of human recombinant leucocyteA interferon (Ro22-8181: -interferon) against 23 human culturedcell lines derived from leukemias and lymphomas was measuredquantitatively by regrowth assay. Daudi cells were the mostsensitive to it. Two T-cell lines (RPMI-8402, HUT78), threeB-cell lines (Raji, Ly16, A3/Kawakami), one non-T, non-B acutelymphoblastic leukemia (ALL) cell line (KOPN-1) and three myelomonocytoidcell lines (U937, THP-1, ML-1) were moderately or slightly sensitive.Although the levels of sensitivity of these cell lines weredifferent, cells could be killed by the recombinant -interferon.Morphological changes in the sensitive cells treated with itwere decreases in mitosis, pyknosis and fragmentation of thecells. Thirteen other cultured cell lines were not sensitive.The results indicated that the growth inhibitory activity ofrecombinant -interferon is not always cell lineage-specific.There were only three cell lines whose sensitivity, expressedby the concentration required for 90% growth inhibition, wasless than the several hundred units per milliliter that hasusually been obtained as blood levels in clinical trials. Thesethree included one of 10 T-cell lines and two of seven B-celllines; none of six non-T, non-B ALL and myelomonocytoid celllines were that sensitive. Among virus-associated cell lines,only Epstein- Barr virus-associated B-cell lines were sensitiveto the interferon; adult T-cell leukemia virus-associated T-celllines were not sensitive. It was demonstrated that recombinant-interferon has a time-dependent, but not a concentration-dependentcytocidal action, indicating that optimal therapeutic schedulesof recombinant -interferon for cancer may be daily long-termtreatment, not single or short-term large-dose therapy.