Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi's sarcoma xenograft.
Blood. 2000 Jun 1;95(11):3506-13. Unique Identifier : AIDSLINE MED/20287391 Husain SR; Puri RK; Laboratory of Molecular Tumor Biology, Division of Cellular and; Gene Therapies, Center for Biologics Evaluation and Research,; Food and Drug Administration, Bethesda, MD 20892, USA.
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 approximately 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 microg/kg per dose) on alternate days (qod) or 5 daily (qd) IT injections with lower doses (50 or 100 microg/kg per dose) resulted in a complete regression of established subcutaneous tumors in most animals. Daily IT treatment with 250 microg/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 microg/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.
Keywords: JOURNAL ARTICLE *Acquired Immunodeficiency Syndrome Animal Dose-Response Relationship, Drug Exotoxins/ADMINISTRATION & DOSAGE/PHARMACOKINETICS/*THERAPEUTIC USE Female Human Immunotoxins/ADMINISTRATION & DOSAGE/PHARMACOKINETICS/ *THERAPEUTIC USE Injections, Intraperitoneal Injections, Intravenous Interleukin-13/*THERAPEUTIC USE Mice Mice, Nude Receptors, Interleukin/DRUG EFFECTS/METABOLISM Sarcoma, Kaposi/*DRUG THERAPY Tumor Cells, Cultured
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
