Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia developed in severe combined immune-deficient mice |
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Authors: | Morland B J Boehm D Flavell S U Kohler J A Flavell D J |
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Institution: | (1) Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, SO9 4XY Southampton, UK;(2) Department of Child Health, Southampton General Hospital, Southampton, UK |
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Abstract: | The transplantation of the human T-cell acute lymphoblastic leukemia (T-ALL) cell line HSB-2 into severe combined immune-deficient
(SCID) mice was found to produce a disseminated pattern of leukemia similar to that seen in humans. The iv injection of 107 HSB-2 cells was associated with a universally fatal leukemia. Histopathological examination of animals revealed the spread
of leukemia initially from bone marrow to involve all major organs including the meninges.
An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 monoclonal antibody (MAb) HB2 to the ribosome inactivating
protein (RIP) saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT)
to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. In an in vivo study, the IT was shown to significantly prolong the survival of SCID mice injected with HSB-2 cells
compared to untreated control animals. This therapeutic effect was seen both with a single injection of 10 μg of IT given
7 d after the injection of HSB-2 cells, and was even more effective when IT was administered as three daily injections of
10 μg on d 7, 8, and 9. These results demonstrate the useful application of human leukemia xenografts in SCID mice and the
potential therapeutic effect of an anti-CD7 IT in human T-ALL. |
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Keywords: | Immunotoxin anti-CD7 monoclonal antibody saporin T-ALL SCID mouse |
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