TAXOL PRETREATMENT OF TUMOR TARGETS AMPLIFIES NATURAL-KILLER-CELL MEDIATED LYSIS

Taxol is known to polymerize and stabilize microtubules and thereby al ter many cellular functions. Our studies examined the effects of taxol pretreatment of tumor targets and cytotoxic effector cells in an effo rt to determine whether such treatment would result in increased tumor cell lysis without affecting cytotoxic cell function. Our studies dem onstrated that taxol concentrations of 6-30 ng/ml which induced simila r to 50% growth inhibition and greater than or equal to 50% block in t he G(2)/M phase of the K562 cell targets did not have any significant effect on the functional ability of NK cells to lyse K562 cells. Pretr eatment of K562 cells with taxol (6 and 30 ng/ml) resulted in an incre ase in K562 cell lysis by NK cells (or NK cells stimulated with 100 un its/ml of rIL-2) in 7 out of 9 donors. The amplification of NK cell-me diated lysis of tumor targets due to taxol pretreatment may provide a combination therapeutic approach which includes taxol treatment follow ed by rIL-2 stimulation of the immune killer cell function.