title: A novel anti-PSMA human scFv has the potential to be used as a diagnostic tool in prostate cancer.
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.
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Jieheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Research & Development, OriMAbs Ltd. Science Center, Philadelphia, PA, 19104, USA.
authors.forename: Yueheng
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Research & Development, Hangzhou Immusource Biotechnology Company, Ltd., Hangzhou, 310010, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Research & Development, OriMAbs Ltd. Science Center, Philadelphia, PA, 19104, USA.
authors.forename: Ruihe
authors.initials: R
authors.lastname: Lin
authors.affiliation: Institute of Molecular Medicine, Nanjing University, Nanjing, 210093, China.
authors.forename: Ziyong
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Fa
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, China.
authors.forename: Dian
authors.initials: D
authors.lastname: Jiao
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: An-Gang
authors.initials: AG
authors.lastname: Yang
authors.affiliation: Department of Research & Development, OriMAbs Ltd. Science Center, Philadelphia, PA, 19104, USA.
authors.forename: Aizhi
authors.initials: A
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Wen
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Qin
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000954:Antigens, Surface; D057127:Single-Chain Antibodies; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: PSMA; diagnostic imaging; prostate cancer; prostate specific membrane antigen; single chain antibody fragment