A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels
| العنوان: | A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels |
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| المؤلفون: | Dario Neri, Francesca Pretto, Cristina M. A. Alonso, Alessandro Palumbo, Piotr Dziunycz, Ross W. Boyle, Kathrin Schwager, F. Hauler, Alex Soltermann, Günther F.L. Hofbauer |
| المساهمون: | University of Zurich |
| المصدر: | British journal of cancer British Journal of Cancer; Vol 104 British Journal of Cancer, 104 (7) British Journal of Cancer |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | squamous cell carcinoma, Cancer Research, Pathology, medicine.medical_specialty, Immunoconjugates, Angiogenesis, medicine.medical_treatment, tumour neovasculature, Population, Fluorescent Antibody Technique, Natural killer cells, Photodynamic therapy, Immunotherapy, Monoclonal antibody, Tumour neovasculature, Squamous cell carcinoma, 610 Medicine & health, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, 10049 Institute of Pathology and Molecular Pathology, medicine, Animals, Humans, 1306 Cancer Research, education, 030304 developmental biology, Mice, Inbred BALB C, 0303 health sciences, education.field_of_study, natural killer cells, Neovascularization, Pathologic, Cancer, 10177 Dermatology Clinic, Neoplasms, Experimental, medicine.disease, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, photodynamic therapy, Photochemotherapy, Oncology, monoclonal antibody, 030220 oncology & carcinogenesis, Heat generation, Cancer cell, Carcinoma, Squamous Cell, 2730 Oncology, immunotherapy, Bone marrow, Translational Therapeutics, Blood vessel |
| الوصف: | Background: The possibility of eradicating cancer by selective destruction of tumour blood vessels may represent an attractive therapeutic avenue, but most pharmaceutical agents investigated so far did not achieve complete cures and are not completely specific. Antibody conjugates now allow us to evaluate the impact of selective vascular shutdown on tumour viability and to study mechanisms of action. Methods: We synthesised a novel porphyrin-based photosensitiser suitable for conjugation to antibodies and assessed anticancer properties of its conjugate with L19, a clinical-stage human monoclonal antibody specific to the alternatively spliced EDB domain of fibronectin, a marker of tumour angiogenesis. Results: Here we show in two mouse model of cancer (F9 and A431) that L19 is capable of highly selective in vivo localisation around tumour blood vessels and that its conjugate with a photosensitiser allows selective disruption of tumour vasculature upon irradiation, leading to complete and long-lasting cancer eradication. Furthermore, depletion experiments revealed that natural killer cells are essential for the induction of long-lasting complete responses. Conclusions: These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis. British Journal of Cancer, 104 (7) ISSN:0007-0920 ISSN:1532-1827 |
| وصف الملف: | Palumbo_et_al_A_chemically_modified_antibody_mediates_complete_eradication_of_tumors-V.pdf - application/pdf; application/application/pdf |
| تدمد: | 0007-0920 1532-1827 |
| DOI: | 10.1038/bjc.2011.78 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c988e1dd9ab01d51bcfd3e29aed102eTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7c988e1dd9ab01d51bcfd3e29aed102e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00070920 15321827 |
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| DOI: | 10.1038/bjc.2011.78 |