Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts
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- Michele Moschetta
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Francesca Pretto
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Alexander Berndt
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Kerstin Galler
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Petra Richter
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Andrea Bassi
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Paolo Oliva
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Edoardo Micotti
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Giovanni Valbusa
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Kathrin Schwager
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Manuela Kaspar
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Eveline Trachsel
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Hartwig Kosmehl
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Maria Rosa Bani
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Dario Neri
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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- Raffaella Giavazzi
- Authors' Affiliations: Departments of 1Oncology and 2Neuroscience, Mario Negri Institute for Pharmacological Research; 3Dipartimento di Fisica, Politecnico di Milano, Milan, Italy; 4Institute of Pathology, University Hospital Jena, Jena, Germany; 5Centro Ricerche Bracco–Bracco Imaging Spa, Colleretto Giacosa, Italy; 6Philochem AG; 7Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland; and 8Institute of Pathology, Helios-Klinikum Erfurt, Erfurt, Germany
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説明
<jats:title>Abstract</jats:title> <jats:p>The selective delivery of bioactive agents to tumors reduces toxicity and enhances the efficacy of anticancer therapies. In this study, we show that the antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn), when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of EDA-Fn–expressing melanomas in combination with paclitaxel. We obtained curative effects with paclitaxel administered before the immunocytokine. Coadministration of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8-IL2–induced natural killer (NK) cells to the tumor, suggesting a host response as part of the observed therapeutic benefit. In support of this likelihood, NK cell depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly, this combination reduced both the tumor burden and the number of pulmonary metastatic nodules. The combination did not cause cumulative toxicity. Together, our findings offer a preclinical proof that by acting on the tumor stroma paclitaxel potentiates the antitumor activity elicited by a targeted delivery of IL2, thereby supporting the use of immunochemotherapy in the treatment of metastatic melanoma. Cancer Res; 72(7); 1814–24. ©2012 AACR.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 72 (7), 1814-1824, 2012-04-01
American Association for Cancer Research (AACR)