Intrapleural Infusion of Activated Macrophages and γ-Interferon in Malignant Pleural Mesothelioma

Monnet, I.; Breau, J. L.; Moro, D.; Léna, H.; Eymard, Jean‐Christophe; Ménard, Olivier; Vuillez, Jean‐Philippe; Chokri, Mohamed Ali; Romet-Lemonne, Jean-Loup; Lopez, M.

doi:10.1378/chest.121.6.1921

Cited by 58 publications

(34 citation statements)

References 30 publications

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“…Immunotherapy for malignant mesothelioma with IFNg and other cytokines (e.g., IL-2) has been investigated in an experimental setting and a clinical trial (34). Local cytokine therapy with recombinant IFN-g administered into the pleural cavity induced some responses in patients with early disease but was ineffective in patients with advanced stage disease (35).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Modulation Enhances the Therapeutic Effect of Anti–IL-13Rα2 Antibody in Human Mesothelioma Xenografts

Takenouchi

Hirai²,

Sakuragi³

et al. 2011

Clinical Cancer Research

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Purpose: The interleukin-13 receptor a2 (IL-13Ra2) is expressed by a variety of human malignant cells. Here, we have examined the constitutive surface expression and the epigenetic regulation of IL-13Ra2 by human mesothelioma. We have also investigated the therapeutic effect of the DNA methylation inhibitor 5-aza-2 0 -deoxycytidine (5-aza-dC) and anti-IL-13Ra2 monoclonal antibody on mesothelioma xenografts.Experimental Design: Cell surface expression of IL-13Ra2 by various lung carcinomas was analyzed using flow cytometry. Therapeutic effects of anti-IL-13Ra2 and 5-aza-dC were investigated using antibodydependent cellular cytotoxicity and proliferation assays and by monitoring the survival of mesotheliomabearing mice.Results: We found that human malignant mesotheliomas expressed surface IL-13Ra2 on their surface and that it was upregulated by treatment with 5-aza-dC. This augmented expression of IL-13Ra2 resulted in growth inhibition of the mesothelioma cells when cocultured with anti-IL-13Ra2 and effector cells, such as splenocytes and peritoneal exudate cells. The growth inhibition of mesothelioma cells was mediated by IFN-g that was only detected in the supernatant when effector cells were exposed to 5-aza-dC-treated tumors in the presence of anti-IL-13Ra2. Compared with the control or either regimen alone, in vivo administration of anti-IL-13Ra2 in combination with 5-aza-dC significantly prolonged the survival of mice with mesothelioma xenografts.Conclusions: These observations indicate a promising role for IL-13Ra2 as a target for antibody treatment in malignant mesothelioma, and, in combination with epigenetic regulation by a DNA methylation inhibitor, suggest the potential for a novel strategy to enhance therapeutic potency.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Modulation Enhances the Therapeutic Effect of Anti–IL-13Rα2 Antibody in Human Mesothelioma Xenografts

Takenouchi

Hirai²,

Sakuragi³

et al. 2011

Clinical Cancer Research

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“…These studies used monocytic cultures generated from relatively small blood samples and resulted in relatively modest numbers of cells for experimental study. Relevant numbers of cytokine stimulating monocytic cells have been generated for clinical trial application [2][3][4][5][6][7][8] and application of these technical methods will be required in order to perform more robust in vivo experiments. However, the basic assay described here clearly demonstrates proof of principle in that low numbers of antigenspecific monocytic cells can effectively modulate the growth of an aggressive tumour cell line in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 In clinical trials, these adoptively transferred cells were well tolerated and showed good trafficking to sites of tumour. [2][3][4][5][6][7][8] Antibody-dependent cellular cytotoxicity (ADCC) is one mechanism that macrophages can employ for direct antitumour activity. [9][10][11] A requirement for ADCC is the generation of tumour-binding antibodies, which can be recognised by macrophages through their Fc receptors.…”

Section: Introductionmentioning

confidence: 99%

Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo

et al. 2006

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Antibody-dependent cellular cytotoxicity (ADCC) is one means by which macrophages (as well as natural killer cells and granulocytes) elicit a cytotoxic response. This is achieved via interaction of the Fc-g-receptor (CD64) with the Fc portion of antibody bound to target cells. We have created a chimeric CD64 molecule that incorporates a single chain Fv molecule, targeted against human carcinoembryonic antigen (CEA), fused to the membrane spanning and cytosolic domains of human CD64. Following adenoviral transfer to primary human monocytes, this chimeric CD64 receptor induced antigen-specific cytokine secretion during culture on immobilised CEA protein or on CEA-expressing tumour cells. Moreover, CEA targeted, but not control, monocytes effectively retarded CEA-positive tumour cell growth in vitro. Importantly, targeted monocyte cultures significantly reduced in vivo tumour growth rates in xenograft studies resulting in improved survival rates over that of control monocyte cultures. These data suggest that genetically directing monocytes against tumour antigens may be a useful means of achieving an immunotherapeutic response. Gene Therapy (2006) 13, 602-610.

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“…The primers were designed using the Primer3 Web site. 4 The annealing temperature of all primers was 58jC. The cDNAs were amplified in 50 AL PCR buffer containing deoxynucleotide triphosphate, MgCl 2 , and the Taq polymerase (Amersham Biosciences, Buckinghamshire, United Kingdom).…”

Section: Methodsmentioning

confidence: 99%

“…Adoptive transfer of activated macrophages is an attractive complement to conventional cancer therapies. Phase I and II studies have shown the feasibility and safety of transfer of IFNg-activated macrophages (MAK cells) in several malignancies, including mesothelioma, ovarian, and bladder cancer (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Distinct Roles for IFN Regulatory Factor (IRF)-3 and IRF-7 in the Activation of Antitumor Properties of Human Macrophages

et al. 2006

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When properly activated, macrophages can be tumoricidal, thus making them attractive additions to standard cancer therapies. To this end, tolerance and activity of human autologous IFN-;-activated macrophages, produced in large scale for clinical use (MAK cells), have been assessed in pilot trials in cancer patients. In the present study, we tested the hypothesis that activation of IFN regulatory factor (IRF)-3 and IRF-7, with subsequent type

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Intrapleural Infusion of Activated Macrophages and γ-Interferon in Malignant Pleural Mesothelioma

Cited by 58 publications

References 30 publications

Epigenetic Modulation Enhances the Therapeutic Effect of Anti–IL-13Rα2 Antibody in Human Mesothelioma Xenografts

Epigenetic Modulation Enhances the Therapeutic Effect of Anti–IL-13Rα2 Antibody in Human Mesothelioma Xenografts

Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo

Distinct Roles for IFN Regulatory Factor (IRF)-3 and IRF-7 in the Activation of Antitumor Properties of Human Macrophages

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