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.
Highlights
The severe combined immunodeficient (SCID) mouse was first described by Bosma et al (1983), who reported its potential for the transplantation of allogeneic haematopoietic cells from Balb/c animals into these animals
There was no obvious lymph node enlargement in any of the animals, one mouse had a large mediastinal tumour similar in character to the mediastinal enlargement seen in some patients with T-cell lymphomas and leukaemias
Our study has demonstrated that the intravenous administration of the human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 into SCID mice produces a disseminated pattern of disease that closely mimics the pattern of disease observed in humans with acute lymphoblastic leukaemia
Summary
The SCID mouse was first described by Bosma et al (1983), who reported its potential for the transplantation of allogeneic haematopoietic cells from Balb/c animals into these animals. Following this study other workers have reported the ability to engraft human lymphoid cells and stem cells to produce normal human lymphoid and myeloid differentiation in these mice (Kamel-Reid & Dick, 1988; McCune et al, 1988; Mosier et al, 1988; Mosier, 1990). This in turn has generated interest in the study of a murine model of AIDS using HIV-I-infected human haematopoietic cells (Namikawa et al, 1988; McCune et al, 1990). Other tumour types including Epstein-Barr virus-associated lymphoproliferative disease (Cannon et al, 1990; Purtillo et al, 1991; Rowe et al, 1991), T-cell lymphoma (Charley et al, 1990; Waller et al, 1991) and lung and other solid carcinomas (Reddy et al, 1987) have been successfully engrafted into SCID mice
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
