Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice

Br J Cancer. 1994 Feb;69(2):279-85. doi: 10.1038/bjc.1994.52.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD / immunology*
  • Antigens, CD7
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Humans
  • Immunotoxins / therapeutic use*
  • In Vitro Techniques
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Leukemia-Lymphoma, Adult T-Cell / therapy*
  • Mice
  • Mice, SCID
  • N-Glycosyl Hydrolases*
  • Neoplasm Transplantation
  • Plant Proteins / therapeutic use*
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD7
  • Antigens, Differentiation, T-Lymphocyte
  • Immunotoxins
  • Plant Proteins
  • Ribosome Inactivating Proteins, Type 1
  • N-Glycosyl Hydrolases
  • Saporins