A recombinant GM-CSF-PE40 ligand toxin is functionally active but not cytotoxic to cells
A granulocyte/macrophage colony‐stimulating factor (GM‐CSF)‐Pseudomonas exotoxin (PE) 40 fusion protein was constructed for potential use in the treatment of myeloid leukaemias, as a conditioning agent prior to allogeneic bone marrow transplantation or for ex vivo purging of malignant cells prior to...
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| Veröffentlicht in: | Immunology and cell biology 1997-06, Vol.75 (3), p.289-294 |
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| creator | O'Brien, Phillipa Smythe, Anne Biggs, James C Smith, Glenn M |
| description | A granulocyte/macrophage colony‐stimulating factor (GM‐CSF)‐Pseudomonas exotoxin (PE) 40 fusion protein was constructed for potential use in the treatment of myeloid leukaemias, as a conditioning agent prior to allogeneic bone marrow transplantation or for ex vivo purging of malignant cells prior to autologous bone marrow transplantation. The GM‐CSF‐PE40 fusion protein successfully binds to the GM‐CSF receptor and is capable of initiating a mitogenic signal similar to native GM‐CSF in the GM‐CSF‐dependent TF1 cell line. The toxin component also appears to be fully functional as determined by an in vitro adenosine diphosphate‐ribosylation assay. The GM‐CSF‐PE4n fusion protein, however, was not cytotoxic to a number of myeloid leukaemia cell lines. It is suggested that the mechanism of internalization of the GM‐CSF receptor is not appropriate for the translocation of PE to the cytosol where it can fulfill its cytotoxic potential. |
| doi_str_mv | 10.1038/icb.1997.44 |
| format | Article |
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The GM‐CSF‐PE40 fusion protein successfully binds to the GM‐CSF receptor and is capable of initiating a mitogenic signal similar to native GM‐CSF in the GM‐CSF‐dependent TF1 cell line. The toxin component also appears to be fully functional as determined by an in vitro adenosine diphosphate‐ribosylation assay. The GM‐CSF‐PE4n fusion protein, however, was not cytotoxic to a number of myeloid leukaemia cell lines. 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| ispartof | Immunology and cell biology, 1997-06, Vol.75 (3), p.289-294 |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Adenosine Diphosphate Ribose - metabolism ADP Ribose Transferases Bacterial Toxins - genetics Bacterial Toxins - metabolism Bacterial Toxins - pharmacology Base Sequence Biological Transport, Active Bone Marrow Purging Bone Marrow Transplantation Cell Death - drug effects cytotoxicity DNA Primers - genetics Exotoxins - genetics Exotoxins - metabolism Exotoxins - pharmacology fusion protein Granulocyte-Macrophage Colony-Stimulating Factor - genetics Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology granulocyte/macrophage colony‐stimulating factor Humans Immunotoxins - genetics Immunotoxins - metabolism Immunotoxins - pharmacology In Vitro Techniques Leukemia, Myeloid - therapy Polymerase Chain Reaction Pseudomonas Pseudomonas aeruginosa Exotoxin A Pseudomonas exotoxin 40 Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Recombinant Fusion Proteins - pharmacology Transplantation Conditioning Tumor Cells, Cultured Virulence Factors |
| title | A recombinant GM-CSF-PE40 ligand toxin is functionally active but not cytotoxic to cells |
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