IN-VITRO COMBINED EFFECTS OF A TRIAZENE COMPOUND AND INTERFERON-BETA ON NATURAL IMMUNITY AGAINST LYMPHOBLASTOID-CELLS - STUDIES AT EFFECTORAND TARGET-CELL LEVEL

It was shown that Dacarbazine and other triazene compounds render muri ne leukemias highly immunogenic and susceptible to natural immunity (N I). In addition a pilot clinical study revealed that Dacarbazine can b e cytotoxic for bone marrow blasts in patients with acute non-lymphobl astic leukemias through a mechanism that could be, at least in part, o f immunological origin. However triazenes depress antigen-dependent re sponses and NI, whereas interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore the complex intera ction between triazenes and IFN on NI effector (i.e. NK) lymphocytes a nd human target lymphoblastoid cells has been investigated. The result s show that: (a) IFN increases NK activity and antagonizes the depress ive effects of methyl-triazene-benzoic acid (MTBA, an in vitro active triazene compound) on the Mt function; (b) a lymphoblastoid cell line exposed to multiple in vitro treatments with MTBA, shows increased gro wth rate, augmented chemoresistance to MTBA, and higher susceptibility to NI than parental cells; (c) as expected IFN pretreatment down-regu lates the susceptibility of lymphoblastoid cells to NK effecters; (d) however a net ''therapeutic gain'' was found if the overall influence of MTBA + IFN on target and effector cells is considered.