In vitro and in vivo prodrug therapy of prostate cancer using anti-γ-Sm-scFv/hCPA fusion protein
Article first published online: 20 FEB 2006
Copyright © 2006 Wiley-Liss, Inc.
Volume 66, Issue 8, pages 858–866, 1 June 2006
How to Cite
Hao, X.-K., Liu, J.-Y., Yue, Q.-H., Wu, G.-J., Bai, Y.-J. and Yin, Y. (2006), In vitro and in vivo prodrug therapy of prostate cancer using anti-γ-Sm-scFv/hCPA fusion protein. Prostate, 66: 858–866. doi: 10.1002/pros.20402
- Issue published online: 21 APR 2006
- Article first published online: 20 FEB 2006
- Manuscript Accepted: 1 DEC 2005
- Manuscript Received: 14 AUG 2005
- National High Technology Research and Development Program of China. Grant Number: 2001AA215321
- Mega-projects of Science Research for the 10th Five-Year Plan. Grant Number: 2002AA2Z3109
- methotrexate (MTX);
- prostate cancer
Raising selectivity to tumor cells is a major challenge for most chemotherapy drugs. One of approaches to realizing this goal is antibody-directed enzyme prodrug therapy (ADEPT). This study was done to investigate the curative effect of a new ADEPT system for the treatment of prostate cancer.
Methotrexate (MTX) prodrugs were synthesized and anti-seminoprotein (SM) single-chain antibody/human carboxypeptidase-A fusion protein (scFv/hCPA) was prepared. Therapeutic effects of this ADEPT system were evaluated.
The synthesis of prodrugs was successful and the prodrugs were confirmed no cytotoxicity, but hydrolysis with tumor-targeted scFv/hCPA fusion protein gave 1,000-fold higher cytotoxicity than MTX-α-Phe only. Cell cycle assays showed that tumor cells were arrested in the S phase after ADEPT treatment; furthermore, tumors were inhibited significantly in scFv/hCPA and MTX-α-Phe treated mice.
Our results suggest that targeted activation cytotoxicity against established prostate cancer by scFv/hCPA mediated ADEPT is tumor-specific and has no systemic toxicity in vitro and in vivo. Prostate 66: 858–866, 2006. © 2006 Wiley-Liss, Inc.