Effect of new investigational drug taxol on oncolytic activity and stimulation of human lymphocytes.
Taxol is a new antineoplastic agent active in the treatment of drug-refractory ovarian and metastatic breast neoplasms. Extensive investigations have been concerned with the effect of taxol on a variety of tumor cells, but there is virtually no information about its effect on human lymphocytes. Since lymphocytes, especially natural killer (NK) cells, have been recognized to play an important role in the body's defense against tumors, we studied the effect of taxol on the cytotoxicity of naive (unstimulated) peripheral blood mononuclear cells (MNCs) and NK cells as well as on these cells' activation and growth in interleukin-2 (IL-2) cultures. We found that taxol impaired the cytotoxicity of naive MNC and NK cells against the NK-sensitive cell line K-562 and against an ovarian cancer cell line, OV-2774, in a concentration-dependent fashion. The highest impairment was observed after incubation of the effector cells with 10 micrograms/ml taxol. In addition, taxol also interfered with the induction of lymphokine-activated cytotoxicity and with lymphocyte growth in IL-2 cultures. However, IL-2 preactivated NK cells displayed substantial levels of cytotoxicity even after taxol treatment. These findings, which indicate that treatment with taxol should follow rather than precede immunotherapeutic intervention, may be important in planning combined chemo- and immunotherapy strategies for cancer patients.
Chuang
L T
LT
Department of General Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Lotzová
E
E
Cook
K R
KR
Cristoforoni
P
P
Morris
M
M
Wharton
J T
JT
D000704:Analysis of Variance; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D017239:Paclitaxel