Sensitivity of fresh leukemic cells to T101 ricin A-chain immunotoxin: a comparative study between Fab fragment and whole Ig conjugates.
We compared the cell killing potency of a whole Ig ricin A-chain immunotoxin (T101 IgG-RTA) against its Fab fragment counterpart (T101 Fab-RTA) on both CEM cells and fresh malignant lymphoid cells. A dye exclusion assay (DEA), was used to evaluate the kinetics of leukaemia cell viability mediated in vitro by each immunotoxin (IT). This study found that in the absence of ammonium chloride (NH4Cl), used as an enhancer agent, T101 Fab-RTA was significantly more toxic to both CEM and fresh leukaemia cells than T101 IgG-RTA. In the presence of NH4Cl (10(-2) M), while no differences could be found between the two IT on CEM cells, T101 Fab-RTA was clearly superior to T101 IgG-RTA on fresh leukaemia cells. These results suggest that T101 Fab-RTA may offer an excellent alternative to T101 IgG-RTA for IT treatment of CD5 positive leukaemia patients.
Chiron
M
M
Laboratoire de Pharmacologie et Toxicologie Fondamentales, CNRS, France.
Derocq
J M
JM
Kuhlein
E
E
Roubinet
F
F
Demur
C
C
Grandjean
H
H
Huguet
F
F
Jaffrezou
J P
JP
Jansen
F
F
Laurent
G
G
D000643:Ammonium Chloride / Q000008:administration & dosage; D002470:Cell Survival; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage; D000922:Immunotoxins / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007938:Leukemia / Q000628:therapy*; D015448:Leukemia, B-Cell / Q000628:therapy; D012276:Ricin / Q000008:administration & dosage*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D000922:Immunotoxins; D000643:Ammonium Chloride; D012276:Ricin