Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate

P. E. Thorpe, D. W. Mason, A. N F Brown, S. J. Simmonds, W. C J Ross, A. J. Cumber, J. A. Forrester

Research output: Contribution to journalArticle

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Abstract

Graft-versus-host disease and marrow graft rejection are two major problems in the treatment of leukaemia with whole body irradiation, high-dose chemotherapy and bone marrow transplantation. Both these problems could be avoided if the patient's own bone marrow could be rendered aleukaemic in vitro and then reinjected into the patient after the radio-chemotherapy had been completed. Here we describe a model system in which lethally irradiated rats were injected with a mixture of bone marrow cells and leukaemic cells and in which the development of leukaemia in the recipient rats was prevented by incubating the cells, before injection, with a monoclonal antibody - ricin conjugate that was selectively toxic to the leukaemic cells. Nonspecific toxicity of the conjugate to haematopoietic stem cells was blocked by carrying out the incubation in the presence of lactose which competitively antagonized the binding of the ricin moiety of the conjugate to galactose residues on the cell surface1-3.

Original languageEnglish (US)
Pages (from-to)594-596
Number of pages3
JournalNature
Volume297
Issue number5867
DOIs
StatePublished - 1982

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Ricin
Bone Marrow
Antibodies
Leukemia
Drug Therapy
Whole-Body Irradiation
Poisons
Graft Rejection
Graft vs Host Disease
Lactose
Hematopoietic Stem Cells
Bone Marrow Transplantation
Radio
Galactose
Bone Marrow Cells
Monoclonal Antibodies
Injections
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Thorpe, P. E., Mason, D. W., Brown, A. N. F., Simmonds, S. J., Ross, W. C. J., Cumber, A. J., & Forrester, J. A. (1982). Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate. Nature, 297(5867), 594-596. https://doi.org/10.1038/297594a0

Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate. / Thorpe, P. E.; Mason, D. W.; Brown, A. N F; Simmonds, S. J.; Ross, W. C J; Cumber, A. J.; Forrester, J. A.

In: Nature, Vol. 297, No. 5867, 1982, p. 594-596.

Research output: Contribution to journalArticle

Thorpe, PE, Mason, DW, Brown, ANF, Simmonds, SJ, Ross, WCJ, Cumber, AJ & Forrester, JA 1982, 'Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate', Nature, vol. 297, no. 5867, pp. 594-596. https://doi.org/10.1038/297594a0
Thorpe PE, Mason DW, Brown ANF, Simmonds SJ, Ross WCJ, Cumber AJ et al. Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate. Nature. 1982;297(5867):594-596. https://doi.org/10.1038/297594a0
Thorpe, P. E. ; Mason, D. W. ; Brown, A. N F ; Simmonds, S. J. ; Ross, W. C J ; Cumber, A. J. ; Forrester, J. A. / Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate. In: Nature. 1982 ; Vol. 297, No. 5867. pp. 594-596.
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