Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer
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Chunsheng Li1,*, Junying Wang1,5,*, Jia Hu1, Yi Feng2, Kosei Hasegawa6, Xiaohui Peng1, Xingmei Duan1, Aizhi Zhao1, John L. Mikitsh4, Vladimir R. Muzykantov3, Ann-Marie Chacko3,4, Daniel A. Pryma4, Steven M. Dunn7, George Coukos1,7
1 Ovarian Cancer Research Center, University of Pennsylvania
2 Department of Cancer Biology, University of Pennsylvania
3 Institute for Translational Medicine and Therapeutics, University of Pennsylvania
4 Nuclear Medicine & Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania
5 Department of Immunology, Norman Bethune College of Medicine Jilin University
6 Saitama International Medical Center Saitama Medical University
7 Ludwig Cancer Research Center, University of Lausanne
* These authors contributed equally to this work
Chunsheng Li, email:
George Coukos, email:
Keywords: scFv, TEM1, endosialin, optical imaging
Received: April 29, 2014 Accepted: July 06, 2014 Published: July 08, 2014
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.
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