Enhancement of the cell-mediated lysis of fresh human leukemia cells by cytostatic drugs.

The in vitro lysis of human leukemia cells by human natural killer cells was enhanced by pretreatment of the leukemia cells with two different cytostatic drugs, which by themselves do not cause lysis of the tumor cells within the time limits of the in vitro assay. Actinomycin D induced this higher susceptibility in four of eight leukemic samples, Cisplatin in three of four samples. Using Actinomycin D pretreatment, no enhanced lysis was seen with lymphocytes and PHA-lymphoblast targets from healthy donors nor with leukemia cell lines. Our results indicate that a larger fraction of leukemia cells than previously detectable can be recognized and destroyed by spontaneous killer cells. Peripheral blood leukemia cells (more than 80% blasts) and mononuclear cells from healthy donors were isolated by density gradient separation and used either directly or stored in liquid nitrogen in the presence of dimethyl sulfoxide. The leukemia cells were incubated with actinomycin D (ActD) or Cisplatin for 2 h, followed by labeling with =lCr in the presence of the respective drugs for 1% h. The leukemia targets were then admixed in microtiter plates with serial dilutions of P-interferon-treated mononuclear cells obtained from healthy donors. The killing exerted by the mononuclear cells was assessed after 6 h of incubation by counting the 51Cr released into the supernatant. Representative values of specific release were taken from the linear portion of the titration curve.