Resistance of myeloid leukaemia cell lines to ricin a-chain immunotoxins

Andreas Engert, Alex Brown, Philip Thorpe

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Nineteen monoclonal antibodies that recognize antigens on myeloid leukaemia cells were screened upon HL60, KGI, U937 and K562 cells for their ability to form effective ricin A-chain immunotoxins. The screening was performed using an indirect assay in which the cells were treated firstly with the test antibody and then with a Fab′ immunotoxin directed against mouse immunoglobulin. Only two antibodies, MEM75 and 120-2A3, both directed against the transferrin receptor (TfR) were predicted to form immunotoxins that would inhibit protein synthesis by the cells by 50% at a concentration (IC50) of 10-8 M or less. This prediction was subsequently confirmed using several of the antibodies directly conjugated to ricin A-chain. By contrast, the same immunotoxins were highly toxic to non-myeloid cells which shared the target antigens. A comparison was made between the rates of endocytosis and degradation by HL60 cells of an anti-TfR immunotoxin 120-2A3 dgA, that was effective at killing myeloid cells, and a CD33 immunotoxin, p67-7·dgA, that bound to myeloid cells but did not kill them. The difference in potency of the two immunotoxins on HL60 cells was not due to deficient uptake of p67-7·dgA but was probably due to the more rapid intracellular degradation of p67-7·dgA. Fast and effective degradation in lysosomes, if a general finding, could explain the poor susceptibility of myeloid cells to ricin A-chain immunotoxins.

Original languageEnglish (US)
Pages (from-to)1079-1086
Number of pages8
JournalLeukemia Research
Volume15
Issue number11
DOIs
StatePublished - 1991

Fingerprint

Ricin
Immunotoxins
Myeloid Leukemia
Myeloid Cells
Cell Line
HL-60 Cells
Transferrin Receptors
Antibodies
Antigens
U937 Cells
K562 Cells
Poisons
Endocytosis
Lysosomes
Inhibitory Concentration 50
Immunoglobulins
Monoclonal Antibodies

Keywords

  • Acute myeloid leukaemia
  • CD33
  • endocytosis
  • immunotoxin
  • ricin A-chain
  • transferrin receptor

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Resistance of myeloid leukaemia cell lines to ricin a-chain immunotoxins. / Engert, Andreas; Brown, Alex; Thorpe, Philip.

In: Leukemia Research, Vol. 15, No. 11, 1991, p. 1079-1086.

Research output: Contribution to journalArticle

Engert, Andreas ; Brown, Alex ; Thorpe, Philip. / Resistance of myeloid leukaemia cell lines to ricin a-chain immunotoxins. In: Leukemia Research. 1991 ; Vol. 15, No. 11. pp. 1079-1086.
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