PMID- 9815666 OWN - NLM STAT- MEDLINE DCOM- 19990216 LR - 20231213 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 3 IP - 2 DP - 1997 Feb TI - 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. PG - 151-6 AB - 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. FAU - Husain, S R AU - Husain SR AD - Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. FAU - Obiri, N I AU - Obiri NI FAU - Gill, P AU - Gill P FAU - Zheng, T AU - Zheng T FAU - Pastan, I AU - Pastan I FAU - Debinski, W AU - Debinski W FAU - Puri, R K AU - Puri RK LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antineoplastic Agents) RN - 0 (Bacterial Toxins) RN - 0 (Exotoxins) RN - 0 (IL13RA1 protein, human) RN - 0 (Immunotoxins) RN - 0 (Interleukin-13) RN - 0 (Interleukin-13 Receptor alpha1 Subunit) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-13) RN - 0 (Virulence Factors) RN - EC 2.4.2.- (ADP Ribose Transferases) SB - IM MH - *ADP Ribose Transferases MH - AIDS-Related Opportunistic Infections/drug therapy/*metabolism MH - Antineoplastic Agents/*pharmacology MH - *Bacterial Toxins MH - Exotoxins/*pharmacology MH - Humans MH - Immunotoxins/immunology/*pharmacology MH - Interleukin-13/*metabolism/pharmacology MH - Interleukin-13 Receptor alpha1 Subunit MH - Protein Synthesis Inhibitors/pharmacology MH - Receptors, Interleukin/*biosynthesis/drug effects MH - Receptors, Interleukin-13 MH - Sarcoma, Kaposi/drug therapy/immunology/*metabolism MH - Tumor Cells, Cultured MH - Tumor Stem Cell Assay MH - *Virulence Factors MH - Pseudomonas aeruginosa Exotoxin A EDAT- 1997/02/01 00:00 MHDA- 1998/11/17 00:01 CRDT- 1997/02/01 00:00 PHST- 1997/02/01 00:00 [pubmed] PHST- 1998/11/17 00:01 [medline] PHST- 1997/02/01 00:00 [entrez] PST - ppublish SO - Clin Cancer Res. 1997 Feb;3(2):151-6.