Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer.

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Version: author
Serval ID
serval:BIB_64D8F7C9B69C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer.
Journal
Oncotarget
Author(s)
Li C., Wang J., Hu J., Feng Y., Hasegawa K., Peng X., Duan X., Zhao A., Mikitsh J.L., Muzykantov V.R., Chacko A.M., Pryma D.A., Dunn S.M., Coukos G.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Publication state
Published
Issued date
2014
Volume
5
Number
16
Pages
6994-7012
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Tumor Endothelial Marker-1 (TEM1/CD248) is a tumor vascular marker with high therapeutic and diagnostic potentials. Immuno-imaging with TEM1-specific antibodies can help to detect cancerous lesions, monitor tumor responses, and select patients that are most likely to benefit from TEM1-targeted therapies. In particular, near infrared(NIR) optical imaging with biomarker-specific antibodies can provide real-time, tomographic information without exposing the subjects to radioactivity. To maximize the theranostic potential of TEM1, we developed a panel of all human, multivalent Fc-fusion proteins based on a previously identified single chain antibody (scFv78) that recognizes both human and mouse TEM1. By characterizing avidity, stability, and pharmacokinectics, we identified one fusion protein, 78Fc, with desirable characteristics for immuno-imaging applications. The biodistribution of radiolabeled 78Fc showed that this antibody had minimal binding to normal organs, which have low expression of TEM1. Next, we developed a 78Fc-based tracer and tested its performance in different TEM1-expressing mouse models. The NIR imaging and tomography results suggest that the 78Fc-NIR tracer performs well in distinguishing mouse- or human-TEM1 expressing tumor grafts from normal organs and control grafts in vivo. From these results we conclude that further development and optimization of 78Fc as a TEM1-targeted imaging agent for use in clinical settings is warranted.
Pubmed
Web of science
Create date
13/02/2015 17:43
Last modification date
20/08/2019 14:21
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