期刊
BRITISH JOURNAL OF CANCER
卷 104, 期 7, 页码 1106-1115出版社
SPRINGERNATURE
DOI: 10.1038/bjc.2011.78
关键词
natural killer cells; photodynamic therapy; immunotherapy; monoclonal antibody; tumour neovasculature; squamous cell carcinoma
类别
资金
- Swiss National Science Foundation [3100A0-105919/1]
- ETH Zurich
- European Union [LSHC-CT-2006-037489, HEALT-F2-2008-201342]
- Swiss Bridge Foundation
- Stammbach Foundation
- Swiss Cancer League
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 (2011) 104, 1106-1115. doi: 10.1038/bjc.2011.78 www.bjcancer.com Published online 8 March 2011 (c) 2011 Cancer Research UK
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据