Potent anti‐tumor effects of an anti‐CD24 ricin A‐chain immunotoxin in vitro and in a disseminated human Burkitt's lymphoma model in SCID mice

• Published in: International journal of cancer Vol. 66; no. 4; pp. 526 - 531
• Main Authors: Schnell, Roland, Katouzi, Ali A., Linnartz, Christoph, Schoen, Gisela, Drillich, Silke, Hansmann, Martin‐Leo, Schiefer, Daniel, Barth, Stefan, Zangemeister‐Wittke, Uwe, Stahel, Rolf A., Diehl, Volker, Engert, Andreas
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 16.05.1996; Wiley-Liss
• Subjects: Animals; Antigens, CD - immunology; Antineoplastic agents; B-Lymphocytes - immunology; Biological and medical sciences; Burkitt Lymphoma - therapy; CD24 Antigen; Cell Survival; General aspects; Humans; Immunotoxins - therapeutic use; Leukemia - immunology; Medical sciences; Membrane Glycoproteins; Mice; Mice, SCID; Neoplasm Transplantation; Pharmacology. Drug treatments; Ricin - administration & dosage; Survival Analysis; Transplantation, Heterologous; Tumor Cells, Cultured; Human origin; Animal model; Immunotoxin; Ricin; Leukemia; Rodentia; Burkitt lymphoma; Malignant hemopathy; B-Lymphocyte; Monoclonal antibody; Peptide chain; Non Hodgkin lymphoma; In vitro; Infection; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Lymphoproliferative syndrome; Viral disease; Established cell line
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19960516)66:4<526::AID-IJC17>3.0.CO;2-5

A new anti‐CD24 immunotoxin (IT), SWA11.dgA, was constructed by coupling the MAb SWA11 via the bivalent linker SMPT to deglycosylated ricin A‐chain (dgA). The effects of SWA11.dgA were evaluated in vitro against the B‐precursor leukemia cell line REH, the non‐B‐non‐T acute lymphoblastic leukemia cell line NALM‐6 and the Burkitt's lymphoma cell lines BL‐2 and BL‐38. Binding of SWA11 to the CD24 antigen was assessed by flow cytometry demonstrating high affinity of the MAb for all cell lines tested. SWA11.dgA inhibited the protein synthesis of BL‐38, NALM‐6, REH and BL‐2 cells by 50% at concentrations (IC50) of 4.0 × 10−11 M, 6.0 × 10−11 M, 8.0 × 10−11 M and 3.0 × 10−9 M, respectively. SWA11.dgA was subsequently used for the treatment of disseminated human BL‐38 Burkitt's lymphoma in a newly developed SCID mouse model. The mean survival time (MST) of BL‐38‐bearing SCID mice was extended from 23 days in untreated controls to more than 230 days when 6 μg SWA11.dgA was applied intraperitoneally one day after tumor challenge. All of the animals achieved continuous complete remissions. SCID mice treated with SWA11.dgA 4 days after tumor cell challenge or a reduced dose of SWAII.dgA (67%) also had a significantly extended MST (45.0 and 51.4 days, respectively, as compared to 22.7 and 23.1 days in the controls). We conclude that SWA11.dgA might be of potential use for the treatment of lymphoma in man. © 1996 Wiley‐Liss, Inc.