DRUG-MEDIATED CHANGES IN THE SUSCEPTIBILITY OF HUMAN LYMPHOBLASTOID B-CELLS TO NK-MEDIATED CYTOLYSIS - STUDIES WITH A TRIAZENE COMPOUND

Previous studies have shown that treatment of leukemia-bearing mice wi th triazene compounds results in a profound alteration of the immunolo gical properties of leukemic cells. These cells become highly immunoge nic and susceptible to natural immunity (NI). Moreover, in a pilot cli nical study, dacarbazine was found to suppress bone marrow blasts in p atients with acute non-lymphoblastic leukemias. The cytotoxic mechanis m involved could be of biochemical and immunological origin as well. T herefore experiments were carried out to test whether triazenes could influence the susceptibility of blast cells to human NI effector lymph ocytes (represented, at least in part, by NK cells). The results obtai ned with target Epstein-Barr virus (EBV)-immortalized B cells and effe ctor cells of different donors, showed that: (a) multiple in vitro tre atments of lymphoblastoid cells with methyl-triazene-benzoic acid (MTB A, a triazene compound active in vitro), gave origin to lines that wer e more resistant than the parental lines to the antitumor effects of M TBA; (b) MTBA-treated lines were more susceptible (37.5% of cases), or less susceptible (31.2% of cases) to NI than parental cells. Effector lymphocytes of various donors recognized different changes in suscept ibility to natural killer (NK)-mediated lysis; (c) treatment of parent al or MTBA-treated lines with interferon-beta reduced target cell susc eptibility to NK-mediated cytolysis, but increased NK activity and lym phoblast chemosensitivity to MTBA.