Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice.
The transplantation of the human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 into severe combined immunodeficient (SCID) mice 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 examination of animals revealed the spread of leukaemia initially from bone marrow to involve all major organs including the meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 MAb HB2 to the ribosome-inactivating protein 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. When SCID mice were injected with 10(6) HSB-2 cells and then treated 8 days later with a single intravenous dose of 10 micrograms of immunotoxin there was a significant therapeutic effect evidenced by the numbers of animals surviving 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.
Morland
B J
BJ
Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, UK.
Barley
J
J
Boehm
D
D
Flavell
S U
SU
Ghaleb
N
N
Kohler
J A
JA
Okayama
K
K
Wilkins
B
B
Flavell
D J
DJ
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D066298:In Vitro Techniques; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D009368:Neoplasm Transplantation; D010940:Plant Proteins / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins