Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells.
Tumors are considered to be possible targets of immunotherapy using stimulated and expanded autologous or allogeneic natural killer (NK) cells mismatched for MHC class I molecules and inhibitory NK receptors. NK cell-based immunoadjuvant therapies are carried out in combination with standard chemotherapeutic protocols. In the presented study, we characterized the effect of 28 frequently used chemotherapeutic agents on the capacity of NK cells to kill target cells. We found that treatment of NK cells with the drugs vinblastine, paclitaxel, docetaxel, cladribine, chlorambucil, bortezomib, and MG-132 effectively inhibited NK cell-mediated killing without affecting the viability of NK cells. On the other hand, the following drugs permitted efficient NK cell-mediated killing even at concentrations comparable with or higher than the maximally achieved therapeutic concentration in vivo in humans: asparaginase, bevacizumab, bleomycin, doxorubicin, epirubicin, etoposide, 5-fluorouracil, hydroxyurea, streptozocin, and 6-mercaptopurine.
Markasz
Laszlo
L
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Box 280, SE-171 77 Stockholm, Sweden.
Stuber
Gyorgy
G
Vanherberghen
Bruno
B
Flaberg
Emilie
E
Olah
Eva
E
Carbone
Ennio
E
Eksborg
Staffan
S
Klein
Eva
E
Skribek
Henriette
H
Szekely
Laszlo
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002857:Chromium / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002857:Chromium