Work

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

Year: 2014

Type: article

Abstract: // Chunsheng Li 1,* , Junying Wang 1,5,* , Jia Hu 1 , Yi Feng 2 , Kosei Hasegawa 6 , Xiaohui Peng 1 , Xingmei Duan 1 , Aizhi Zhao 1 , John L. Mikitsh 4 , Vladimir R. Muzykantov 3 , Ann-Marie Chacko 3,4 , Daniel A. Pryma 4 , Steven M. Dunn 7 , George Coukos 1,7 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 Correspondence: Chunsheng Li, email: // George Coukos, email: // Keywords : scFv, TEM1, endosialin, optical imaging Received : April 29, 2014 Accepted : July 06, 2014 Published : July 08, 2014 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.2188