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Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft model

Nature Medicine volume 5, pages 817–822 (1999)Cite this article

Abstract

The elusive and enigmatic origin of AIDS-associated Kaposi's sarcoma (AIDS-KS) makes it a complex tumor and therefore difficult to treat. Here we demonstrate that AIDS-KS cells express surface interleukin-4 (IL-4) receptors, and that IL-4 toxin (IL-4(38-37)-PE38KDEL) is specifically cytotoxic to these cells. Intratumoral, intraperitoneal and intravenous administration of IL-4 toxin in nude mice with established subcutaneous AIDS-KS tumors caused considerable anti-tumor activity in a dose-dependent manner, with highest dose producing durable complete responses. Metabolic changes, including cachexia and lymphopenia, induced by KS tumors were prevented by IL-4 toxin treatment. This report establishes IL-4(38-37)-PE38KDEL as an experimental therapeutic agent for the treatment of AIDS-KS.

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Figure 1: IL-4 receptor expression on AIDS-KS cells.
Figure 2: Cytotoxicity of IL-4 toxin against AIDS-KS cells.
Figure 3: Dose-dependent anti-tumor activity of IL-4 toxin in AIDS-KS xenografts.
Figure 4: Complete eradication of AIDS-KS tumors by intratumor injection of IL-4 toxin.
Figure 5: Prevention of cachexia induced by AIDS-KS tumors.

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Acknowledgements

We thank J. Kassis and D. Essayan for reading the manuscript. We are indebted to P. Dover for technical assistance and procurement of reagents.

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Authors and Affiliations

  1. Division of Cellular and Gene Therapies, Laboratory of Molecular Tumor Biology, Center for Biologics Evaluation and Research, FDA, Bethesda, 20892, Maryland, USA

    Syed R. Husain & Raj K. Puri

  2. Division of Basic Sciences, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Robert J. Kreitman & Ira Pastan

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  1. Syed R. Husain
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Correspondence to Raj K. Puri.

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Husain, S., Kreitman, R., Pastan, I. et al. Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft model. Nat Med 5, 817–822 (1999). https://doi.org/10.1038/10541

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