A high-affinity human antibody that targets tumoral blood vessels

Lorenzo Tarli, Enrica Balza, Francesca Viti, Laura Borsi, Patrizia Castellani, Dietmar Berndorff, Ludger Dinkelborg, Dario Neri, Luciano Zardi

Research output: Contribution to journalArticle

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Abstract

Angiogenesis is a characteristic feature of many aggressive tumors and of other relevant disorders. Molecules capable of specifically binding to new-forming blood vessels, but not to mature vessels, could be used as selective vehicles and would, therefore, open diagnostic and therapeutic opportunities. We have studied the distribution of the ED-B oncofetal domain of fibronectin, a marker of angiogenesis, in four different tumor animal models: the F9 murine teratocarcinoma, SKMEL-28 human melanoma, N592 human small cell lung carcinoma, and C51 human colon carcinoma. In all of these experimental models we observed accumulation of the fibronectin isoform containing the ED-B domain around neovascular structures when the tumors were in the exponentially growing phase, but not in the slow-growing phase. Then we performed biodistribution studies in mice bearing a subcutaneously implanted F9 murine teratocarcinoma, using a high-affinity human antibody fragment (L19) directed against the ED-B domain of fibronectin. Radiolabeled L19, but not an irrelevant anti-lysozyme antibody fragment (D1.3), efficiently localizes in the tumoral vessels. The maximal dose of L19 accumulated in the tumor was observed 3 hours after injection (8.2% injected dose per gram). By virtue of the rapid clearance of the antibody fragment from the circulation, tumor-to-blood ratios of 1.9, 3.7, and 11.8 were obtained at 3, 5, and 24 hours, respectively. The tumor-targeting performance of L19 was not dose-dependent in the 0.7 to 10 μg range of injected antibody. The integral of the radioactivity localized in tumoral vessels over 24 hours was greater than 70-fold higher than the integral of the radioactivity in blood over the same time period, normalized per gram of tissue or fluid. These findings quantitatively show that new-forming blood vessels can selectively be targeted in vivo using specific antibodies, and suggest that L19 may be of clinical utility for the immunoscintigraphic detection of angiogenesis in patients.

Original languageEnglish
Pages (from-to)192-198
Number of pages7
JournalBlood
Volume94
Issue number1
Publication statusPublished - Jul 1 1999

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Antibody Affinity
Blood vessels
Blood Vessels
Tumors
Immunoglobulin Fragments
Antibodies
Fibronectins
Teratocarcinoma
Neoplasms
Radioactivity
Blood
Bearings (structural)
Small Cell Lung Carcinoma
Muramidase
Anti-Idiotypic Antibodies
Melanoma
Protein Isoforms
Colon
Animals
Theoretical Models

ASJC Scopus subject areas

  • Hematology

Cite this

Tarli, L., Balza, E., Viti, F., Borsi, L., Castellani, P., Berndorff, D., ... Zardi, L. (1999). A high-affinity human antibody that targets tumoral blood vessels. Blood, 94(1), 192-198.

A high-affinity human antibody that targets tumoral blood vessels. / Tarli, Lorenzo; Balza, Enrica; Viti, Francesca; Borsi, Laura; Castellani, Patrizia; Berndorff, Dietmar; Dinkelborg, Ludger; Neri, Dario; Zardi, Luciano.

In: Blood, Vol. 94, No. 1, 01.07.1999, p. 192-198.

Research output: Contribution to journalArticle

Tarli, L, Balza, E, Viti, F, Borsi, L, Castellani, P, Berndorff, D, Dinkelborg, L, Neri, D & Zardi, L 1999, 'A high-affinity human antibody that targets tumoral blood vessels', Blood, vol. 94, no. 1, pp. 192-198.
Tarli L, Balza E, Viti F, Borsi L, Castellani P, Berndorff D et al. A high-affinity human antibody that targets tumoral blood vessels. Blood. 1999 Jul 1;94(1):192-198.
Tarli, Lorenzo ; Balza, Enrica ; Viti, Francesca ; Borsi, Laura ; Castellani, Patrizia ; Berndorff, Dietmar ; Dinkelborg, Ludger ; Neri, Dario ; Zardi, Luciano. / A high-affinity human antibody that targets tumoral blood vessels. In: Blood. 1999 ; Vol. 94, No. 1. pp. 192-198.
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