title: Effects of an anti HLA-DR immunotoxin on leukaemia cells and hematopoietic progenitors.
abstract: 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.
authors.affiliation: Laboratoire de hématologie et génétique, Centre de Transfusion Sanguine, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Demur
authors.forename: J M
authors.initials: JM
authors.lastname: Derocq
authors.forename: P
authors.initials: P
authors.lastname: Poncelet
authors.forename: M
authors.initials: M
authors.lastname: Chiron
authors.forename: F
authors.initials: F
authors.lastname: Roubinet
authors.forename: J P
authors.initials: JP
authors.lastname: Jaffrezou
authors.forename: C
authors.initials: C
authors.lastname: Bordier
authors.forename: G
authors.initials: G
authors.lastname: Laurent
mesh_terms: 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
chemical_list: D006684:HLA-DR Antigens; D000922:Immunotoxins; D012276:Ricin