Interleukin-13 receptor as a unique target for anti-glioblastoma therapy

Husain, Syed R.; Joshi, Bharat; Puri, Raj K.

doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1182>3.0.co;2-n

Cited by 124 publications

(71 citation statements)

References 21 publications

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“…administrations of IL-13 cytotoxin were needed for pronounced antitumor activity, we examined the extent of apoptosis by this schedule, which has also shown marked antitumor activity in many solid tumor xenograft models including Kaposi's sarcoma, glioblastoma and other head-and-neck tumors. [1][2][3][4][5][6][7] Mice were injected with 100 g/kg of IL-13 cytotoxin in established tumors on days 4, 6 and 8; then, tumor size, caspase activity and apoptotic cells were determined. Tumors were resected 6 hr after each IL-13 cytotoxin injection for caspase and apoptotic cell assay.…”

Section: Accumulation Of Apoptotic Molecules In Scchn Tumors Treated mentioning

confidence: 99%

“…[1][2][3][4][5][6][7] To target these receptors, a recombinant IL-13R-targeted cytotoxin (IL-13PE38, also termed IL-13 cytotoxin) consisting of 2 major components, recombinant human IL-13 and a mutated form of PE, was generated. Over the years, we have shown that IL-13 cytotoxin is extremely cytotoxic to tumor cell lines that express IL-13R in vitro and in vivo.…”

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confidence: 99%

“…Over the years, we have shown that IL-13 cytotoxin is extremely cytotoxic to tumor cell lines that express IL-13R in vitro and in vivo. [1][2][3][4][5][6][7] Based on preclinical studies, we have begun phase I clinical trials for possible treatment of recurrent malignant glioma and advanced renal cell carcinoma. 8,9 To understand the mechanism of cell death caused by IL-13 cytotoxin, we have demonstrated that IL-13 cytotoxin can mediate apoptosis in headand-neck tumor cell lines in vitro.…”

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confidence: 99%

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Tumor regression mechanisms by IL‐13 receptor–targeted cancer therapy involve apoptotic pathways

Kawakami

Puri

2002

Intl Journal of Cancer

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Section: Accumulation Of Apoptotic Molecules In Scchn Tumors Treated mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Tumor regression mechanisms by IL‐13 receptor–targeted cancer therapy involve apoptotic pathways

Kawakami

Puri

2002

Intl Journal of Cancer

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“…26,32 IL-13 cytotoxin is composed of IL-13 and a truncated form of Pseudomonas exotoxin, and has been shown to have a potent antitumor activity in vitro 25,26,29,32,33 and in vivo 25,27,30,34 in many tumor models. Through extensive targeting studies, it has become apparent that there is a difference in sensitivity to IL-13 cytotoxin of many cancer types.…”

Section: Introductionmentioning

confidence: 99%

Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor α2 chain in vivo

Kawakami

Husain

et al. 2003

Gene Ther

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Interleukin-13 receptor (IL-13R) a2 chain plays a key role in ligand binding and internalization. We have recently demonstrated that this cytokine receptor chain has unique characteristics in tumor biology: it inhibits tumorigenicity of breast and pancreatic cancer in animal models. In this study, we have exploited IL-13Ra2 chain and established a novel approach for pancreatic cancer therapy. For this, a plasmid encoding the IL-13Ra2 chain gene was mixed with liposomes and injected into subcutaneously or orthotopically xenografted human pancreatic tumors in immunodeficient mice, followed by systemic or local therapy by a recombinant IL-13 cytotoxin. Only tumors forced to express IL-13Ra2 chain acquired extreme susceptibility to the antitumor effect of IL-13 cytotoxin. There was a dominant infiltration of cells including macrophages and natural killer cells in the regressing tumors. Since macrophages were found to produce nitric oxide, IL-13Ra2-targeted cancer therapy involved not only a direct tumor cell killing by IL-13 cytotoxin but also activation of innate immune response at the tumor site. Therefore, this approach may be a new powerful tool for pancreatic cancer or other localized cancer therapy.

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“…Previous studies have proved that IL-13 cytotoxin is highly selective and potent in killing cancer cells that overexpress IL-13R 2 chain. 3,[5][6][7][8][9][10][11][12]14,16,17 Preclinical studies regarding the safety and toxicity of IL-13 cytotoxin have been performed in mice, rats and monkeys; and all animals tolerated this therapy well, with minimal toxicity to vital organs. 18 Based on these results, 3 phase I/II clinical trials of this cytotoxin in adults with malignant glioma have been initiated, and all are currently ongoing in the United States.…”

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confidence: 99%

Adenoviral vector–mediated gene transfer of IL‐13Rα2 chain followed by IL‐13 cytotoxin treatment offers potent targeted therapy for cytotoxin‐resistant cancers

Saitô

Murata

Watanabe

et al. 2005

Intl Journal of Cancer

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Previous studies demonstrated that IL-13Ra2 chain-overexpressing cancer cells were highly sensitive to IL-13 cytotoxin (IL13-PE38QQR) and could be targeted by cytotoxin treatment. However, the majority of human tumors do not express high levels of IL-13Ra2 chain. To expand the IL-13 cytotoxin-mediated cancer targeting therapy, we combined cytotoxin treatment with gene transfer of IL-13Ra2 chain. We constructed a recombinant adenoviral vector carrying the human IL-13Ra2 gene (Ad-IL-13Ra2), which expresses high levels of IL-13Ra2 chain on infected cells. Human cancer cell lines A549 and HOS, which originally show no IL-13Ra2 expression and little sensitivity to IL-13 cytotoxin, were effectively converted to become sensitive to this cytotoxin after Ad-IL-13Ra2 infection. The CC 50 of IL-13 cytotoxin for Ad-IL13Ra2-infected A549 cells was <10 ng/ml, whereas the CC 50 for uninfected or control vector-infected cells was >500 ng/ml. We also examined the antitumor activity of IL-13 cytotoxin in an established xenograft model of cytotoxin-resistant human lung tumor. Only a single i.t. injection of Ad-IL-13Ra2 markedly enhanced the sensitivity of established tumors to IL-13 cytotoxin treatment; furthermore, this antitumor effect was significantly sustained for more than 1 month after the last treatment with IL-13 cytotoxin. Taken together, these results suggest the combination of adenoviral vector-mediated IL-13Ra2 gene transfer and IL-13 cytotoxin administration can be an effective targeting approach for several types of IL-13 cytotoxin-resistant cancers which show no or little expression of IL-13Ra2 chain. ' 2005 Wiley-Liss, Inc.

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Interleukin-13 receptor as a unique target for anti-glioblastoma therapy

Cited by 124 publications

References 21 publications

Tumor regression mechanisms by IL‐13 receptor–targeted cancer therapy involve apoptotic pathways

Tumor regression mechanisms by IL‐13 receptor–targeted cancer therapy involve apoptotic pathways

Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor α2 chain in vivo

Adenoviral vector–mediated gene transfer of IL‐13Rα2 chain followed by IL‐13 cytotoxin treatment offers potent targeted therapy for cytotoxin‐resistant cancers

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