Enhanced in vitro cytotoxicity of 1,3-bis-(2-chloroethyl)-1-nitrosourea or buthionine sulfoximine combined with a reactive oxygen-generating enzyme immunotoxin.
The glutathione inhibitor drugs, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and buthionine sulfoximine (BSO), were tested in vitro in order to assess their cytotoxic effectiveness when combined with an enzyme immunotoxin (eIT) composed of a T-cell reactive monoclonal antibody (mAb) 097 coupled to the reactive oxygen-generating enzyme, glucose oxidase (GO) (EC 1.1.3.4). As targets of this eIT we used mature human T-cells or leukemia cells that expressed the 097 epitope. We found that treatment of the cells with subtoxic amounts of mixtures of both a drug and the 097 eIT markedly potentiated cytotoxicity compared to either drug or eIT alone.
Ito
H
H
Laboratoire d'Immunologie, UPR 6, CNRS, Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
Rousseau
V
V
Goavec
M
M
Beaujean
F
F
Morizet
J
J
Stanislawski
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols; D019328:Buthionine Sulfoximine; D002330:Carmustine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005949:Glucose Oxidase; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007784:Lactoperoxidase; D008223:Lymphoma / Q000188:drug therapy; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects
D000922:Immunotoxins; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005949:Glucose Oxidase; D007784:Lactoperoxidase; D005978:Glutathione; D002330:Carmustine