Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi's sarcoma xenograft

Clinically advanced and rapidly progressive AIDS-associated Kaposi sarcoma (AIDS-KS) tumors require an aggressive tumor-directed therapy. We have obse rved that AIDS-KS cells express high levels of receptors for immune regulat ory cytokine, interleukin-13 (IL-13). Two tumorigenic AIDS-KS cell lines, K S Y-1 and KS-imm, expressed 4560 and 9480 IL-13 binding sites per cell with an affinity (kd) of similar to 0.9 and 3.7 nmol/L, respectively. IL-13 cyt otoxin IL13-PE38QQR, consisting of human IL-13 and a derivative of Pseudomo nas exotoxin, is specifically cytotoxic to KS tumor cells. Systemic and loc o regional administration of IL13-PE38QQR in immunodeficient mice with esta blished human KS tumors produced remarkable antitumor activity. Three intra tumoral (IT) injections of IL-13 toxin (250 mu g/kg per dose) on alternate days (qod) or 5 daily (qd) IT injections with lower doses (50 or 100 mu g/k g per dose) resulted in a complete regression of established subcutaneous t umors in most animals. Daily IT treatment with 250 mu g/kg of IL-13 toxin i n another KS-derived cell line also produced complete responses. Twice dail y intraperitoneal injections of IL13-PE38QQR (25 or 50 mu g/kg per dose) fo r 10 days (total injections = 20) also completely eradicated KS Y-1 tumors, Intravenous administration of IL13-PE38QQR also suppressed tumor growth; h owever, complete responses were not observed. All animals tolerated the the rapeutic doses of IL-13 toxin without any visible signs of toxicity. The ef ficacy of receptor-directed IL13-PE38QQR therapy in mice warrants further e xploration of this drug for AIDS-KS treatment. (Blood, 2000;95: 3506-3513) (C) 2000 by The American Society of Hematology.