Taxol pretreatment of tumor targets amplifies natural killer cell mediated lysis.
Taxol is known to polymerize and stabilize microtubules and thereby alter many cellular functions. Our studies examined the effects of taxol pretreatment of tumor targets and cytotoxic effector cells in an effort to determine whether such treatment would result in increased tumor cell lysis without affecting cytotoxic cell function. Our studies demonstrated that taxol concentrations of 6-30 ng/ml which induced approximately 50% growth inhibition and > or = 50% block in the G2/M phase of the K562 cell targets did not have any significant effect on the functional ability of NK cells to lyse K562 cells. Pretreatment of K562 cells with taxol (6 and 30 ng/ml) resulted in an increase in K562 cell lysis by NK cells (or NK cells stimulated with 100 units/ml of rIL-2) in 7 out of 9 donors. The amplification of NK cell-mediated lysis of tumor targets due to taxol pretreatment may provide a combination therapeutic approach which includes taxol treatment followed by rIL-2 stimulation of the immune killer cell function.
Mehta
S
S
Department of Surgery, Roger Williams Medical Center, Brown University,Providence, Rhode Island 02908, USA.
Blackinton
D
D
Manfredi
M
M
Rajaratnam
D
D
Kouttab
N
N
Wanebo
H
H
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D016015:Logistic Models; D008938:Mitosis / Q000187:drug effects*; D017239:Paclitaxel / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel