Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia developed in severe combined immune-deficient mice.
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.
Morland
B J
BJ
Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, UK.
Boehm
D
D
Flavell
S U
SU
Kohler
J A
JA
Flavell
D J
DJ
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000922:Immunotoxins