We have previously shown that human renal cell carcinoma (RCC) cells express large numbers of interleukin-13 receptors (IL-13R), a newly described hemopoietic growth factor receptor. To target tumor cells that express IL-13R, we have produced a chimeric protein composed of human IL-13 and a derivative of Pseudomonas exotoxin A, termed PE38QQR. We report here that IL13-PE38QQR is highly cytotoxic to many human RCC cell lines. IL-13R-negative cell lines or cell lines expressing low numbers of IL-13R ( < 300 sites/cell) that include human bone marrow- derived cells were not susceptible to the cytotoxic effect of IL 13- PE38QQR. The sensitivity of RCC cells to IL13-PE38QQR correlated positively with the density of IL-13R. The cytotoxic activity of IL13- PE38QQR was competed by an excess of IL-13 in a protein synthesis inhibition assay and confirmed by a clonogenic assay. Even though IL-13 and IL-4 are homologues and IL-4R and IL-13R have been proposed to share a receptor subunit, IL-4 did not compete for the cytotoxicity mediated by IL13-toxin on RCC. IL13-PE38QQR competes for [125I]-IL-13 binding sites on RCC cells, although at a lower affinity than the wild- type recombinant cytokine. Human T-cell, B-cell, and monocytic cell lines are unresponsive to the cytotoxic action of IL13-PE38QQR. Thus, our results indicate that IL13-PE38QQR is highly cytotoxic to human RCC cells, although it is not cytotoxic to a variety of normal hematopoietic cells. IL13-PE38QQR should be further investigated preclinically for the treatment of human RCCs.
ARTICLES|
May 15, 1996
Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR)
RK Puri,
RK Puri
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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P Leland,
P Leland
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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NI Obiri,
NI Obiri
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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SR Husain,
SR Husain
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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RJ Kreitman,
RJ Kreitman
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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GP Haas,
GP Haas
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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I Pastan,
I Pastan
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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W Debinski
W Debinski
Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
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Blood (1996) 87 (10): 4333–4339.
Citation
RK Puri, P Leland, NI Obiri, SR Husain, RJ Kreitman, GP Haas, I Pastan, W Debinski; Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR). Blood 1996; 87 (10): 4333–4339. doi: https://doi.org/10.1182/blood.V87.10.4333.bloodjournal87104333
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