Bj. Morland et al., EFFECTIVENESS OF HB2 (ANTI-CD7) - SAPORIN IMMUNOTOXIN IN AN IN-VIVO MODEL OF HUMAN T-CELL LEUKEMIA DEVELOPED IN SEVERE COMBINED IMMUNODEFICIENT MICE, British Journal of Cancer, 69(2), 1994, pp. 279-285
The transplantation of the human T-cell acute lymphoblastic leukaemia
(T-ALL) cell line HSB-2 into severe combined immunodeficient (SCID) mi
ce was found to produce a disseminated pattern of leukaemia similar to
that seen in man. The intravenous injection of 10(7) HSB-2 cells was
associated with a universally fatal leukaemia. Histopathological exami
nation of animals revealed the spread of leukaemia initially from bone
marrow to involve all major organs including the meninges. An immunot
oxin (HB2-Sap) was constructed by conjugating the anti-CD7 MAb HB2 to
the ribosome-inactivating protein saporin. An in vitro protein synthes
is inhibition assay revealed specific delivery of HB2-Sap immmunotoxin
(IT) to CD7(+) HSB-2 target cells with an IC50 of 4.5 pM. When SCID m
ice were injected with 10(6) HSB-2 cells and then treated 8 days later
with a single intravenous dose of 10 mu g of immunotoxin there was a
significant therapeutic effect evidenced by the numbers of animals sur
viving in the therapy group compared with untreated controls (chi 2 =
5.348, P = 0.021). These results demonstrate the useful application of
human leukaemia xenografts in SCID mice and the potential therapeutic
effect of an anti-CD7 immunotoxin in human T-ALL.