Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia developed in severe combined immune-deficient mice.

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 10(7) 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 micrograms 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 micrograms 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.

• Authors: B J Morland, D Boehm, S U Flavell, J A Kohler, D J Flavell
• Journal: Cell biophysics (Cell Biophys) Vol. 24-25 Pg. 315-29 ( 1994) ISSN: 0163-4992 [Print] United States
• PMID: 7736537 (Publication Type: Journal Article)

Chemical References

• Immunotoxins

Topics

• Animals
• Cytotoxicity Tests, Immunologic
• Disease Models, Animal
• Humans
• Immunotoxins (therapeutic use)
• Leukemia-Lymphoma, Adult T-Cell (therapy)
• Mice
• Mice, SCID
• Neoplasm Transplantation
• Tumor Cells, Cultured