RECEPTOR FOR INTERLEUKIN-13 ON AIDS-ASSOCIATED KAPOSIS-SARCOMA CELLS SERVES AS A NEW TARGET FOR A POTENT PSEUDOMONAS EXOTOXIN-BASED CHIMERIC TOXIN PROTEIN

AIDS-associated Kaposi's sarcoma (AIDS-KS), the most common malignant complication of human immunodeficiency virus infection, is characteriz ed by neoplastic proliferation of mesenchymal cells, AIDS-KS cells rel ease and respond to an array of cytokines through specific plasma memb rane receptors, Specific targeting of potent cytotoxic agents to cell surface receptors/antigens on Kaposi's sarcoma cells may provide effec tive therapy for this malignancy, We have identified a new target in t he form of an interleukin 13 (IL-13) receptor that is overexpressed in the five AIDS-KS cell lines examined. Radio-labeled IL-13 cross-linke d to a single protein of about M-r 70,000 in AIDS KS cells, We utilize d a chimeric cytotoxic protein composed of IL-13 and a truncated Pseud omonas 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 significa nt antitumor activity in a human epidermoid carcinoma xenograft model. Normal human umbilical vein-derived endothelial, lymphoid, and bone m arrow 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 ce lls may represent a novel plasma membrane protein(s) that could be uti lized to target therapeutic agents.