A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels

Autor: 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
Přispěvatelé: University of Zurich
Rok vydání: 2011
Předmět:
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
Zdroj: British journal of cancer
British Journal of Cancer; Vol 104
British Journal of Cancer, 104 (7)
British Journal of Cancer
ISSN: 0007-0920
1532-1827
DOI: 10.1038/bjc.2011.78
Popis: 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
Databáze: OpenAIRE
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