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