Effects of an anti HLA-DR immunotoxin on leukaemia cells and hematopoietic progenitors.
An anti HLA-class II immunotoxin has been prepared by coupling to ricin A-chain (RTA) and anti-DR-DP monoclonal antibody (2G5-MoAb). Protein synthesis inhibition assays showed that 2G5-RTA immunotoxin is: highly cytotoxic to B-cell lymphoid neoplastic cells, and variable so to ALL cells, while AML cell lines display a generally poor susceptibility. Toxicity of 2G5-RTA on normal hematopoietic cells (HPC) was found to be dose-dependent, and to increase significantly with the addition of NH4Cl, used as an activating agent. After 4 h of incubation with 2G5-RTA (10(-8) M), without NH4Cl, percentages of CFU-GM and CFU-GEMM (colony forming units-granulo-monocytes and -multipotent, respectively) progenitor cell recovery were in the order of 50% and 30% respectively. In the same treatment conditions, 2G5-RTA induced a 6 log kill on RAJI cells--measured by clonogenic assay. Finally, this study shows that anti-DR immunotoxins may represent an original, efficient, and relatively safe approach for bone marrow purging of DR positive malignant B-cell populations; while their clinical potential pertaining to ALL and AML remains uncertain.
Demur
C
C
Laboratoire de hématologie et génétique, Centre de Transfusion Sanguine, Toulouse, France.
Derocq
J M
JM
Poncelet
P
P
Chiron
M
M
Roubinet
F
F
Jaffrezou
J P
JP
Bordier
C
C
Laurent
G
G
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006684:HLA-DR Antigens / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007938:Leukemia / Q000276:immunology / Q000473:pathology*; D051379:Mice; D010641:Phenotype; D012276:Ricin / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D006684:HLA-DR Antigens; D000922:Immunotoxins; D012276:Ricin