Modulation of antitumoral antibody-dependent cellular cytotoxicity and natural killer activity by Adriamycin and daunorubicin

Mouse effector cells isolated from various anatomical sources failed to mediate antibody-dependent cellular cytotoxicity (ADCC) against alloantiserum-coated L1210 murine leukemia cell targets, whereas rat spleen cells appeared to be potent mediators of this activity. Following suppression of effector cell function 3 days after a single drug injection, the nylon wool non-adherent population of rat spleen cells from daunorubicin (DM)-treated rats demonstrated an increased ability to mediate ADCC compared to controls. Alternatively, although suppression occurred at day 7, no rebound enhancement was demonstrated by the same cell population isolated from Adriamycin (AM)-treated animals for as long as 12 days post-injection. Natural killer (NK) activity, measured as the ability of the nylon wool non-adherent rat spleen cell population to lyse uncoated L1210 cells, was modulated by drug treatment in a similar manner at each time point although the changes were not significant. In contrast to NK cells for which a substantial amount of activity remained adherent to nylon wool, all K cell activity was found in the non-adherent spleen cell population. The effector cell, in both cases, was not susceptible to antithymocyte serum plus complement treatment; however, NK activity appeared trypsin-sensitive whereas K cell activity did not. Therefore, AM and DM demonstrated different activities with regard toin vivo modulation of antitumoral ADCC.Supported in part by PHS Grant 5T32 GM07230 and a grant from the National Cancer Institute.