Effectiveness of combinations of bispecific antibodies for delivering saporin to human acute T-cell lymphoblastic leukaemia cell lines via CD7 and CD38 as cellular target molecules.
We have investigated the effectiveness of three different F(ab' gamma)2 bispecific antibodies (BsAb) for delivering the ribosome inactivating protein (RIP) saporin via the CD7 or CD38 cell surface molecules to the human T-ALL cell lines HSB-2 and HPB-ALL. Inhibition of 3H-leucine uptake by target cells was used as the parameter of cellular cytotoxicity. Used singly against HSB-2 cells in the presence of varied concentrations of saporin, an anti-CD7 BsAb, (HB2 x DB7-18) and an anti-CD38 BsAb (OKT10 x RabSap), gave 435- and 286-fold increases in saporin toxicity, respectively. For HPB-ALL cells the anti-CD7 BsAb performed poorly giving only an eight-fold increase in toxicity whilst on the same cell line the anti-CD38 BsAb was highly potent giving an 80,000-fold increase in saporin toxicity. A combination of both BsAb used together against HSB-2 cells was ten times more effective, than the best single BsAb HB2 x DB7-18 used alone. Kinetic studies conducted with HSB-2 cells revealed that the BsAb combination also gave an increased rate of protein synthesis inactivation in comparison to either BsAb used alone. These investigations clearly demonstrate a synergistic action when both BsAb are used in combination to target saporin against CD7 and CD38 expressed on the surface of the HSB-2 cell line.
Simon Flavell Leukaemia Research Laboratory, University Department of Pathology, Southampton, UK.
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Flavell
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Cooper
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Morland
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French
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Flavell
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000276:immunology; D019011:Antigens, CD7; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins / Q000008:administration & dosage; D066298:In Vitro Techniques; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000276:immunology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000008:administration & dosage*; D014176:Protein Biosynthesis; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects; D000076985:Saporins; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D019011:Antigens, CD7; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1