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.