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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3506-3513
Interleukin-13 fusion cytotoxin as a potent targeted agent for
AIDS-Kaposi's sarcoma xenograft
Syed R. Husain and
Raj K. Puri
From the Laboratory of Molecular Tumor Biology, Division of Cellular
and Gene Therapies, Center for Biologics Evaluation and Research, Food
and Drug Administration, Bethesda, MD 20892.
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.
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