Oncotarget

Research Papers:

A novel anti-PSMA human scFv has the potential to be used as a diagnostic tool in prostate cancer

Donghui Han, Jieheng Wu, Yueheng Han, Ming Wei, Sen Han, Ruihe Lin, Ziyong Sun, Fa Yang, Dian Jiao, Pin Xie, Lingling Zhang, An-Gang Yang, Aizhi Zhao, Weihong Wen and Weijun Qin _

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Oncotarget. 2016; 7:59471-59481. https://doi.org/10.18632/oncotarget.10697

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Abstract

Donghui Han1,*, Jieheng Wu2,*, Yueheng Han3, Ming Wei4, Sen Han5, Ruihe Lin3, Ziyong Sun6, Fa Yang1, Dian Jiao4, Pin Xie1, Lingling Zhang2, An-Gang Yang2, Aizhi Zhao3, Weihong Wen2, Weijun Qin1

1Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi’an, China

2State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi’an, China

3Department of Research & Development, OriMAbs Ltd. Science Center, Philadelphia, PA, 19104, USA

4Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi’an, China

5Department of Research & Development, Hangzhou Immusource Biotechnology Company, Ltd., Hangzhou, 310010, China

6Institute of Molecular Medicine, Nanjing University, Nanjing, 210093, China

*These authors have contributed equally to this work

Correspondence to:

Weijun Qin, email: qinweij@fmmu.edu.cn

Weihong Wen, email: wenweih@fmmu.edu.cn

Aizhi Zhao, email: zhaoaizhi@orimabs.com

Keywords: prostate cancer, prostate specific membrane antigen, PSMA, single chain antibody fragment, diagnostic imaging

Received: December 15, 2015     Accepted: June 09, 2016     Published: July 19, 2016

ABSTRACT

Prostate cancer (PCa) is the most commonly diagnosed malignancy and the second leading cause of cancer related death in men. The early diagnosis and treatment of PCa are still challenging due to the lack of efficient tumor targeting agents in traditional managements. Prostate specific membrane antigen (PSMA) is highly expressed in PCa, while only has limited expression in other organs, providing an ideal target for the diagnosis and therapy of PCa. The antibody library technique has opened the avenue for the discovery of novel antibodies to be used in the diagnosis and therapy of cancer. In this paper, by screening a large yeast display naive human single chain antibody fragment (scFv) library, we obtained a high affinity scFv targeting PSMA, called gy1. The gy1 scFv was expressed in E.coli and purified via a C terminal 6His tag. The binding affinity of gy1 was shown to be at the nanomolar level and gy1 can specifically bind with PSMA positive cancer cells, and binding triggers its rapid internalization through the endosome-lysosome pathway. The specific targeting of gy1 to PSMA positive tumor tissues was also evaluated in vivo. We showed that the IRDye800CW labeled gy1 can efficiently target and specifically distribute in PSMA positive tumor tissues after being injected into xenograft nude mice. This study indicated that the novel antibody gy1 could be used as a great tool for the development of PSMA targeted imaging and therapy agents for PCa.


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