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MAbs. 2012 Nov-Dec;4(6):775-83. doi: 10.4161/mabs.22271. Epub 2012 Oct 2.

Biodistribution studies with tumor-targeting bispecific antibodies reveal selective accumulation at the tumor site.

Author information

1
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology ETH Zürich, Zurich, Switzerland.

Abstract

Bispecific antibodies are proteins that bind two different antigens and may retarget immune cells with a binding moiety specific for a leukocyte marker. A binding event in blood could in principle prevent antibody extravasation and accumulation at the site of disease. In this study, we produced and characterized two tetravalent bispecific antibodies that bind with high affinity to the alternatively-spliced EDB domain of fibronectin, a tumor-associated antigen. The bispecific antibodies simultaneously engaged the cognate antigens (murine T cell co-receptor CD3 and hen egg lysozyme) and selectively accumulated on murine tumors in vivo. The results, which were in agreement with predictions based on pharmacokinetic modeling and antibody binding characteristics, confirmed that bispecific antibodies can reach abluminal targets without being blocked by peripheral blood leukocytes.

KEYWORDS:

antibody; biodistribution; bispecific; syngeneic; tumor

PMID:
23032949
PMCID:
PMC3502244
DOI:
10.4161/mabs.22271
[Indexed for MEDLINE]
Free PMC Article

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