Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

被引：29

作者：

El-Emir, E.

Dearling, J. L. J.

Huhalov, A.

Robson, M. P.

Boxer, G.

Neri, D.

van Dongen, G. A. M. S.

Trachsel, E.

Begent, R. H. J.

Pedley, R. B.

机构：

[1] UCL Royal Free & Univ Coll, Sch Med, Dept Oncol, Canc Res UK Targeting & Imaging Grp, London NW3 2PF, England

[2] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland

[3] Vrije Univ Amsterdam, Med Ctr, Dept Otolaryngol Head & Neck Surg, NL-1081 HV Amsterdam, Netherlands

来源：

BRITISH JOURNAL OF CANCER | 2007年 / 96卷 / 12期

关键词：

L19-SIP; radioimmunotherapy; ED-B; vasculature; tumour;

D O I：

10.1038/sj.bjc.6603806

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Angiogenesis is a characteristic feature of tumours and other disorders. The human monoclonal antibody L19-SIP targets the extra domain B of fibronectin, a marker of angiogenesis expressed in a range of tumours. The aim of this study was to investigate whole body distribution, tumour localisation and the potential of radioimmunotherapy with the L19-small immunoprotein (SIP) in colorectal tumours. Two colorectal tumour models with highly different morphologies, the SW1222 and LS174T xenografts, were used in this study. Localisation and retention of the L19-SIP antibody at tumour vessels was demonstrated using immunohistochemistry and Cy3-labelled L19-SIP. Whole body biodistribution studies in both tumour models were carried out with I-125-labelled L19-SIP. Finally, I-131-labelled antibody was used to investigate the potential of radioimmunotherapy in SW1222 tumours. Using immunohistochemistry, we confirmed extra domain B expression in the tumour vasculature. Immunofluorescence demonstrated localisation and retention of injected Cy3-labelled L19-SIP at the abluminal side of tumour vessels. Biodistribution studies using a I-125-labelled antibody showed selective tumour uptake in both models. Higher recorded values for localisation were found in the SW1222 tumours than in the LS174T (7.9 vs 6.6 %vertical bar D g(-1)), with comparable blood clearance for both models. Based on these results, a radioimmunotherapy study was performed in the SW1222 xenograft using I-131-Labelled L19-SIP (55.5 MBq), which showed selective tumour uptake, tumour growth inhibition and improved survival. Radio-and fluorescence-labelled L19-SIP showed selective localisation and retention at vessels of two colorectal xenografts. Furthermore, I-131-L19-SIP shows potential as a novel treatment of colorectal tumours, and provides the foundation to investigate combined therapies in the same tumour models.

引用

页码：1862 / 1870

页数：9

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