[Specific cytotoxicity of recombinant interleukin 6-pseudomonas exotoxin fusion protein (IL6-PE40) on LT12 leukemic cells expressing high levels of interleukin 6 receptor (IL6R)].
An acute promyelocytic leukemic cell line LT12 was transduced with IL6R cDNA by electroporation. The resultant LT12-IL6R+ leukemic cells expressed more than 1000 IL6R per cell. The effect of the recombinant IL6-PE40 on both the LT12-IL6R+ cells and the IL6R- parental cells (LT12-IL6R-) was studied by leukemic progenitor colony (CFU-L) formation and 3H-TdR incorporation assays. It was found that IL6-PE40 at concentrations ranging from 1 to 1,000 ng/ml inhibited CFU-L formation and DNA synthesis of LT12-IL6R+ cells in a dose-dependent manner. No inhibition was seen at the same concentration range in LT12-IL6R- cells. At concentrations of 250-1000ng/ml, IL6-PE40 led to only 40% inhibition of DNA synthesis in LT12-IL6R- cells. Inasmuch as rIL6 at the same concentrations had no significant effect on both IL6R+ and IL6R- cells, we concluded it is IL6-PE40 that exerts its highly specific killing on leukemic cells expressing high levels of IL6R.
Xi
Y Z
YZ
Institute of Basic Medical Sciences, CAMS, Beijing.
D036002:ADP Ribose Transferases; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000096:biosynthesis; D018274:Electroporation; D005098:Exotoxins / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D011549:Pseudomonas; D051381:Rats; D011914:Rats, Inbred BN; D018123:Receptors, Interleukin / Q000235:genetics*; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D001426:Bacterial Proteins; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D005098:Exotoxins; C064195:IL-6-PE40 protein, chimeric; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D036002:ADP Ribose Transferases