Comparison of the potency and therapeutic efficacy of the anti-CD7 immunotoxin HB2-saporin constructed with one or two saporin moieties per immunotoxin molecule.
Immunotoxins that carry two toxin molecules to the target cell should in theory have a greater anti-tumour effect than those that carry just one. We have investigated the therapeutic efficacy of two anti-CD7-saporin immunotoxins constructed with one saporin (HB2-Sap 1-mer) or two saporin molecules (HB2-Sap 2-mer) per immunotoxin molecule. In vitro, the 2-mer immunotoxin was 5.6 times more effective than the 1-mer immunotoxin at inhibiting protein synthesis in the CD7+ human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 and was also more effective at inhibiting HSB-2 cell proliferation. Flow cytometry revealed that the 2-mer immunotoxin had a reduced binding capacity to HSB-2 cells compared with the 1-mer immunotoxin or native HB2 antibody. In therapy studies in SCID mice with disseminated HSB-2 human leukaemia, the 2-mer immunotoxin performed marginally better than the 1-mer immunotoxin, but log-rank analysis did not reveal any significant differences between the two therapy groups. We therefore conclude that, although the 2-mer immunotoxin performed better than the 1-mer immunotoxin against target HSB-2 cells in vitro, this improved performance was not reflected as an improved in vivo therapeutic outcome in the SCID mouse model.
Flavell
D J
DJ
The Simon Flavell Leukaemia Research Laboratory, University Department of Pathology, Southampton General Hospital, UK.
Boehm
D A
DA
Noss
A
A
Flavell
S U
SU
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D019011:Antigens, CD7 / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010940:Plant Proteins / Q000008:administration & dosage*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D000911:Antibodies, Monoclonal; D019011:Antigens, CD7; D000922:Immunotoxins; D009363:Neoplasm Proteins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins