Sensitivity of c-erbB positive cells to a ligand toxin and its utility in purging breast cancer cells from peripheral blood stem cell (PBSC) collections.
Autografting following high-dose conditioning is being increasingly offered to breast cancer sufferers, without due regard to the reinfusion of malignant cells. We sought to determine if a breast cancer cell line could be successfully purged from peripheral blood stem cell (PBSC) harvests using a ligand-toxin molecule directed to heregulin-activated erbB receptors. Initial experiments demonstrated no reduction in hemopoietic colony-forming ability in the presence of ligand toxin (2 nM). Breast cancer cell lines which demonstrated differing sensitivities to the ligand toxin were subsequently seeded into stem cell collections and incubated with 2 nM ligand-toxin. One cell line, ZR-75-1, was completely sensitive to the ligand toxin in this mixture; a second, MDB-MA-361, was more profoundly sensitive to the ligand toxin in the presence of the PBSC, whereas a third was unaffected by the toxin. These results suggest purging may indeed be possible in the PBSC of breast cancer patients, but the parameters that define sensitivity are as yet unknown.
Keir
M
M
Haematology Research Laboratory, St. Vincent's Hospital, Sydney, NSW, Australia.
Fiddes
R
R
Biggs
J C
JC
Kearney
P P
PP
D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D066246:ErbB Receptors / Q000378:metabolism*; D005098:Exotoxins / Q000494:pharmacology*; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D066246:ErbB Receptors; D005098:Exotoxins; D006023:Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins; C101006:HAR-TX beta 2 protein, recombinant; C587689:ERBB4 protein, human