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Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein.

S R Husain, N I Obiri, P Gill, T Zheng, I Pastan, W Debinski and R K Puri
S R Husain
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N I Obiri
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P Gill
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T Zheng
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I Pastan
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W Debinski
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R K Puri
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DOI:  Published February 1997
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Abstract

AIDS-associated Kaposi's sarcoma (AIDS-KS), the most common malignant complication of human immunodeficiency virus infection, is characterized by neoplastic proliferation of mesenchymal cells. AIDS-KS cells release and respond to an array of cytokines through specific plasma membrane receptors. Specific targeting of potent cytotoxic agents to cell surface receptors/antigens on Kaposi's sarcoma cells may provide effective therapy for this malignancy. We have identified a new target in the form of an interleukin 13 (IL-13) receptor that is overexpressed in the five AIDS-KS cell lines examined. Radiolabeled IL-13 cross-linked to a single protein of about Mr 70,000 in AIDS-KS cells. We utilized a chimeric cytotoxic protein composed of IL-13 and a truncated Pseudomonas exotoxin (IL13-PE38QQR), which was found to be specifically and highly cytotoxic to AIDS-KS cells, as determined by protein synthesis inhibition and clonogenic assays. IL13-PE38QQR demonstrated significant antitumor activity in a human epidermoid carcinoma xenograft model. Normal human umbilical vein-derived endothelial, lymphoid, and bone marrow precursor cells expressed low levels of IL-13 receptors, and IL-13 toxin was not cytotoxic to them. Thus, IL-13 receptor on AIDS-KS cells may represent a novel plasma membrane protein(s) that could be utilized to target therapeutic agents.

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February 1997
Volume 3, Issue 2
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Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein.
S R Husain, N I Obiri, P Gill, T Zheng, I Pastan, W Debinski and R K Puri
Clin Cancer Res February 1 1997 (3) (2) 151-156;

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Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein.
S R Husain, N I Obiri, P Gill, T Zheng, I Pastan, W Debinski and R K Puri
Clin Cancer Res February 1 1997 (3) (2) 151-156;
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Clinical Cancer Research
eISSN: 1557-3265
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