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.
MeSH terms
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ADP Ribose Transferases*
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Acquired Immunodeficiency Syndrome / complications*
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Animals
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Bacterial Toxins*
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Cachexia / prevention & control
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Exotoxins / therapeutic use*
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Humans
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Immunotoxins / therapeutic use*
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Interleukin-4 / therapeutic use*
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Lymphopenia / prevention & control
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Mice
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Mice, Nude
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Peptide Fragments / therapeutic use
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Receptors, Interleukin-4 / drug effects
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Receptors, Interleukin-4 / physiology*
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Recombinant Fusion Proteins / therapeutic use
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Sarcoma, Kaposi / drug therapy*
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Sarcoma, Kaposi / etiology
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Sarcoma, Kaposi / immunology
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Sarcoma, Kaposi / physiopathology
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Transplantation, Heterologous
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Tumor Cells, Cultured
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Virulence Factors*
Substances
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Bacterial Toxins
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Exotoxins
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Immunotoxins
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Peptide Fragments
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Receptors, Interleukin-4
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Recombinant Fusion Proteins
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Virulence Factors
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interleukin 4 (38-37)-PE38KDEL
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Interleukin-4
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ADP Ribose Transferases
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toxA protein, Pseudomonas aeruginosa