A novel fully human antibody targeting extracellular domain of psma inhibits tumor growth in prostate cancer

Jieheng Wu, Donghui Han, Shengjia Shi, Qiang Zhang, Guoxu Zheng, Ming Wei, Yueheng Han, Guodong Li, Fa Yang, Dian Jiao, Pin Xie, Lingling Zhang, An Gang Yang, Aizhi Zhao, Weijun Qin, Weihong Wen*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related death. It is of vital importance to develop new strategies for prostate cancer therapy. PSMA (prostate-specific membrane antigen) is specifically expressed in prostate cancer and the neovasculature of certain cancer types, thus is considered to be an ideal target for cancer therapy. In our previous study, we have obtained a PSMA-specific single-chain variable fragment (scFv), named gy1, from a large yeast display na€ve human scFv library. In this study, we reconstructed the PSMA scFv into a fully human antibody (named PSMAb) and evaluated its characterization both in vitro and in vivo. We showed that PSMAb can specifically bind with and internalize into PSMAþ cells. The binding affinity of PSMAb is measured to be at nanomolar level, and PSMAb has very good thermostability. In vivo study showed that near IR dye–labeled PSMAb can specifically localize at PSMAþ tumors, and the application of PSMAb in vivo significantly inhibited the growth of PSMAþ tumors, but not PSMA tumors. At the studied doses, no obvious toxicity was observed when applied in vivo, as shown by the relative normal liver and kidney function and normal structure of important organs, shown by hematoxylin and eosin staining. In addition, PSMAb may inhibit tumor growth through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity mechanisms. Our results indicated that the novel fully human antibody, PSMAb, deserve further study for PSMA-targeted diagnosis and therapy for prostate cancer and other cancer types with vascular PSMA expression.

Original languageEnglish (US)
Pages (from-to)1289-1301
Number of pages13
JournalMolecular cancer therapeutics
Volume18
Issue number7
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wu, J., Han, D., Shi, S., Zhang, Q., Zheng, G., Wei, M., Han, Y., Li, G., Yang, F., Jiao, D., Xie, P., Zhang, L., Yang, A. G., Zhao, A., Qin, W., & Wen, W. (2019). A novel fully human antibody targeting extracellular domain of psma inhibits tumor growth in prostate cancer. Molecular cancer therapeutics, 18(7), 1289-1301. https://doi.org/10.1158/1535-7163.MCT-18-1078