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

Abstract

Abstract Clinically advanced and rapidly progressive AIDS-associated Kaposi sarcoma (AIDS-KS) tumors require an aggressive tumor-directed therapy. We have observed that AIDS-KS cells express high levels of receptors for immune regulatory cytokine, interleukin-13 (IL-13). Two tumorigenic AIDS-KS cell lines, KS Y-1 and KS-imm, expressed 4560 and 9480 IL-13 binding sites per cell with an affinity (kd) of ∼0.9 and 3.7 nmol/L, respectively. IL-13 cytotoxin IL13-PE38QQR, consisting of human IL-13 and a derivative of Pseudomonas exotoxin, is specifically cytotoxic to KS tumor cells. Systemic and loco regional administration of IL13-PE38QQR in immunodeficient mice with established human KS tumors produced remarkable antitumor activity. Three intratumoral (IT) injections of IL-13 toxin (250 μg/kg per dose) on alternate days (qod) or 5 daily (qd) IT injections with lower doses (50 or 100 μg/kg per dose) resulted in a complete regression of established subcutaneous tumors in most animals. Daily IT treatment with 250 μg/kg of IL-13 toxin in another KS-derived cell line also produced complete responses. Twice daily intraperitoneal injections of IL13-PE38QQR (25 or 50 μg/kg per dose) for 10 days (total injections = 20) also completely eradicated KS Y-1 tumors. Intravenous administration of IL13-PE38QQR also suppressed tumor growth; however, complete responses were not observed. All animals tolerated the therapeutic doses of IL-13 toxin without any visible signs of toxicity. The efficacy of receptor-directed IL13-PE38QQR therapy in mice warrants further exploration of this drug for AIDS-KS treatment.