title: Comparison of the performance of anti-CD7 and anti-CD38 bispecific antibodies and immunotoxins for the delivery of saporin to a human T-cell acute lymphoblastic leukemia cell line.
abstract: We have investigated the cytotoxic performance of two different anti-CD7/anti-saporin BsAb's (HB2 x DB7-18 and Q1.1), three anti-CD38/anti-saporin BsAb's (OKT10 x RabSap, OKT10 x DB7-18 and Q4.1) and an anti-CD7 (HB2-Sap) and anti-CD38-saporin (OKT10-Sap) immunotoxin for delivering the ribosome inactivating protein (rip) to the human T-cell acute lymphoblastic leukemia cell line HSB-2. In the case of CD7 as target molecule the immunotoxin outperformed both anti-CD7 BsAb's being six times more effective than HB2 x DB7-18 and 98 times more so than Q1.1 at effectively inhibiting protein synthesis in a dose dependent manner. The chemically constructed HB2 x DB7-18 BsAb was more effective at inhibiting protein synthesis and cell growth in target HSB-2 cells in a dose dependent manner than the quadroma produced BsAb Q1.1. Both BsAb demonstrated a prozone effect used at concentrations above 0.1 nM though this was more pronounced for Q1.1 than for HB2 x DB7-18. The prozone effect was partially though not completely reversed by increasing the concentration of saporin in the system. In the case of CD38 as target molecule the anti-CD38 IT OKT10-Sap performed poorly, never actually achieving its IC50. Two BsAb's constructed with monoclonal anti-saporin Fab arms each recognizing a different epitope on the saporin molecule also performed poorly. In contrast the BsAb OKT10 x RabSap constructed with Fab derived from a rabbit polyclonal anti-saporin antiserum performed in a dose dependent manner achieving its IC50 at a concentration of 1.3 nM. This BsAb also exhibited a prozone effect. These results exemplify the importance of cross linking adjacent target molecules on the cell surface in order to achieve effective delivery of saporin to the cell interior.
authors.affiliation: Simon Flavell Leukaemia Research Laboratory, University Department of Pathology, Southampton General Hospital, U.K.
authors.forename: D J
authors.initials: DJ
authors.lastname: Flavell
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.forename: K
authors.initials: K
authors.lastname: Okayama
authors.forename: L
authors.initials: L
authors.lastname: Emery
authors.forename: S U
authors.initials: SU
authors.lastname: Flavell
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D018033:Antibodies, Bispecific; D015703:Antigens, CD; D019011:Antigens, CD7 / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division; D004337:Drug Carriers; D006801:Humans; D000922:Immunotoxins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000276:immunology; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000276:immunology; D010940:Plant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured
chemical_list: D018033:Antibodies, Bispecific; D015703:Antigens, CD; D019011:Antigens, CD7; D000943:Antigens, Differentiation; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D000922:Immunotoxins; D008562:Membrane Glycoproteins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; 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