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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-03-08

AUTHORS

A Palumbo, F Hauler, P Dziunycz, K Schwager, A Soltermann, F Pretto, C Alonso, G F Hofbauer, R W Boyle, D Neri

ABSTRACT

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. More... »

PAGES

1106-1115

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2011.78

DOI

http://dx.doi.org/10.1038/bjc.2011.78

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020004152

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21386847


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98 skin
99 squamous cell carcinoma
100 therapeutic avenues
101 therapy
102 tumor angiogenesis
103 tumor blood vessels
104 tumor cell death
105 tumor vasculature
106 tumor viability
107 tumors
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109 vasculature
110 vessels
111 viability
112 vivo localisation
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