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
✍ Scribed by Roland Schnell; Ali A. Katouzi; Christoph Linnartz; Gisela Schoen; Silke Drillich; Martin-Leo Hansmann; Daniel Schiefer; Stefan Barth; Uwe Zangemeister-Wittke; Rolf A. Stahel; Volker Diehl; Andreas Engert
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 859 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
A new anti-CD24 immunotoxin (IT), SWAl l.dgA, was constructed by coupling the MAb SWAl I via the bivalent linker SMPT to deglycosylated r i c h A-chain (dgA). The effects of SWAl I .dgA were evaluated in vitro against the B-precursor leukemia cell line REH, the non-6-non-T acute lymphoblastic leukemia cell line NALM-6 and the Burkitt's lymphoma cell lines BL-2 and EL-38. Binding of SWAl I to the CD24 antigen was assessed by flow cytometry demonstrating high affinity of the MAb for all cell lines tested. SWAl l.dgA inhibited the protein synthesis of BL-38, NALM-6, REH and BL-2 cells by 50% at concentrations (ICso) of 4.0 X lo-" M, 6.0 X lo-" M, 8.0 X lo-" M and 3.0 X M, respectively. SWAI I.dgA was subsequently used for the treatment of disseminated human BL-38 Burkitt's lymphoma in a newly developed SClD mouse model. The mean survival time (MST) of EL-38-bearing SClD mice was extended from 23 days in untreated controls to more than 230 days when 6 pg SWAl I .dgA was applied intraperitoneally one day after tumor challenge. All of the animals achieved continuous complete remissions. SClD mice treated with SWAl I .dgA 4 days after tumor cell challenge or a reduced dose of SWAl l.dgA (67%) also had a significantly extended MST (45.0 and 5 I .4 days, respectively, as compared to 22.7 and 23. I days in the controls). We conclude that SWA I I .dgA might be of potential use for the treatment of lymphoma in man.