Targeted antitumor prodrug therapy using CNGRC-yCD fusion protein in combination with 5-fluorocytosine

详细信息    查看全文

• 作者：Jia-Je Li ; Shun-Fu Chang ; I-Iu Liau ; Pei-Chia Chan…
• 关键词：Targeted cancer therapy ; Aminopeptidase N ; Asparagine ; glycine ; arginine motif ; Cytosine deaminase ; 5 ; fluorocytosine ; 5 ; fluorouracil
• 刊名：Journal of Biomedical Science
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：23
• 期：1
• 全文大小：1,453 KB
• 参考文献：1.Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31.CrossRef PubMed
  2.Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.CrossRef PubMed
  3.Pasquier E, Kavallaris M, André N. Metronomic chemotherapy: new rationale for new directions. Nat Rev Clin Oncol. 2010;7:455–65.CrossRef PubMed
  4.Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005;438:967–74.CrossRef PubMed
  5.Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473:298–307.PubMedCentral CrossRef PubMed
  6.Mina-Osorio P. The moonlighting enzyme CD13: old and new functions to target. Trends Mol Med. 2008;14:361–71.CrossRef PubMed
  7.Corti A, Curnis F, Rossoni G, Marcucci F, Gregorc V. Peptide-mediated targeting of cytokines to tumor vasculature: the NGR-hTNF example. BioDrugs. 2013;27(6):591–603.PubMedCentral CrossRef PubMed
  8.Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A, et al. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res. 2000;60:722–7.PubMedCentral PubMed
  9.Fukasawa K, Fujii H, Saitoh Y, Koizumi K, Aozuka Y, Sekine K, et al. Aminopeptidase N (APN/CD13) is selectively expressed in vascular endothelial cells and plays multiple roles in angiogenesis. Cancer Lett. 2006;243:135–43.CrossRef PubMed
  10.Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 1998;279:377–80.CrossRef PubMed
  11.Ellerby HM, Arap W, Ellerby LM, Kain R, Andrusiak R, Rio GD, et al. Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med. 1999;5:1032–8.CrossRef PubMed
  12.Persigehl T, Ring J, Bremer C, Heindel W, Holtmeier R, Stypmann J, et al. Non-invasive monitoring of tumor-vessel infarction by retargeted truncated tissue factor tTF-NGR using multi-modal imaging. Angiogenesis. 2014;17:235–46.CrossRef PubMed
  13.Bieker R, Kessler T, Schwöppe C, Padró T, Persigehl T, Bremer C, et al. Infarction of tumor vessels by NGR-peptide-directed targeting of tissue factor: experimental results and first-in-man experience. Blood. 2009;113:5019–27.CrossRef PubMed
  14.Van Hensbergen Y, Broxterman HJ, Elderkamp YW, Lankelma J, Beers JC, Heijn M, et al. A doxorubicin-CNGRC-peptide conjugate with prodrug properties. Biochem Pharmacol. 2002;63:897–908.CrossRef PubMed
  15.Von Wallbrunn A, Waldeck J, Höltke C, Zühlsdorf M, Mesters R, Heindel W, et al. In vivo optical imaging of CD13/APN-expression in tumor xenografts. J Biomed Opt. 2008;13:011007.CrossRef PubMed
  16.Hahnenkamp A, Schäfers M, Bremer C, Höltke C. Design and synthesis of small-molecule fluorescent photoprobes targeted to aminopeptdase N (APN/CD13) for optical imaging of angiogenesis. Bioconjug Chem. 2013;24:1027–38.CrossRef PubMed
  17.Guillen KP, Kurkjian C, Harrison RG. Targeted enzyme prodrug therapy for metastatic prostate cancer - a comparative study of L-methioninase, purine nucleoside phosphorylase, and cytosine deaminase. J Biomed Sci. 2014;21:65.PubMedCentral CrossRef PubMed
  18.Van Rite BD, Harrison RG. Annexin V-targeted enzyme prodrug therapy using cytosine deaminase in combination with 5-fluorocytosine. Cancer Lett. 2011;307:53–61.CrossRef PubMed
  19.Miller CR, Williams CR, Buchsbaum DJ, Gillespie GY. Intratumoral 5-fluorouracil produced by cytosine deaminase/5-fluorocytosine gene therapy is effective for experimental human glioblastomas. Cancer Res. 2002;62:773–80.PubMed
  20.Lan KH, Shih YS, Chang CA, Yen SH, Lan KL. 5-Fluorocytosine combined with Fcy-hEGF fusion protein targets EGFR-expressing cancer cells. Biochem Biophys Res Commun. 2012;428:292–7.CrossRef PubMed
  21.Hamstra DA, Rice DJ, Fahmy S, Ross BD, Rehemtulla A. Enzyme/Prodrug Therapy for Head and Neck Cancer Using a Catalytically Superior Cytosine Deaminase. Hum Gene Ther. 1999;10:1993–2003.CrossRef PubMed
  22.Kievit E, Bershad E, Ng E, Sethna P, Dev I, Lawrence TS, et al. Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts. Cancer Res. 1999;59:1417–21.PubMed
  23.Nyati MK, Symon Z, Kievit E, Dornfeld KJ, Rynkiewicz SD, Ross BD, et al. The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer model. Gene Ther. 2002;9:844–9.CrossRef PubMed
  24.Lv SQ, Zhang KB, Zhang EE, Gao FY, Yin CL, Huang CJ, et al. Antitumor efficiency of the cytosine deaminase/5-fluorocytosine suicide gene therapy system on malignant gliomas: an in vivo study. Med Sci Monit. 2009;15:BR13–20.PubMed
  25.Chen CT, Yamaguchi H, Lee HJ, Du Y, Lee HH, Xia W, et al. Dual targeting of tumor angiogenesis and chemotherapy by endostatin-cytosine deaminase-uracil phosphoribosyltransferase. Mol Cancer Ther. 2011;10:1327–36.PubMedCentral CrossRef PubMed
  26.Bhagwat SV, Lahdenranta J, Giordano R, Arap W, Pasqualini R, Shapiro LH. CD13/APN is activated by angiogenic signals and is essential for capillary tube formation. Blood. 2001;97:652–9.PubMedCentral CrossRef PubMed
  27.Majumdar S, Siahaan TJ. Peptide-mediated targeted drug delivery. Med Res Rev. 2012;32:637–58.CrossRef PubMed
  28.Chen L, Lin YL, Peng G, Li F. Structural basis for multifunctional roles of mammalian aminopeptidase N. Proc Natl Acad Sci U S A. 2012;109:17966–71.PubMedCentral CrossRef PubMed
  29.Wickström M, Larsson R, Nygren P, Gullbo J. Aminopeptidase N (CD13) as a target for cancer chemotherapy. Cancer Sci. 2011;102:501–8.CrossRef PubMed
  30.Liu C, Yang Y, Chen L, Lin YL, Li F. A unified mechanism for aminopeptidase N-based tumor cell motility and tumor-homing therapy. J Biol Chem. 2014;289:34520–9.PubMedCentral CrossRef PubMed
  31.Curnis F, Arrigoni G, Sacchi A, Fischetti L, Arap W, Pasqualini R, et al. Differential binding of drugs containing the NGR motif to CD13 isoforms in tumor vessels, epithelia, and myeloid cells. Cancer Res. 2002;62:867–74.PubMed
  32.Curnis F, Sacchi A, Borgna L, Magni F, Gasparri A, Corti A. Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol. 2000;18:1185–90.CrossRef PubMed
  33.Corti A, Curnis F. Tumor vasculature targeting through NGR peptide-based drug delivery systems. Curr Pharm Biotechnol. 2011;12:1128–34.CrossRef PubMed
  34.Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3:330–8.CrossRef PubMed
  
• 作者单位：Jia-Je Li (1) (2)
  Shun-Fu Chang (3)
  I-Iu Liau (1)
  Pei-Chia Chan (1)
  Ren-Shyan Liu (1) (4) (6)
  Sang-Hue Yen (1) (5)
  Hsin-Ell Wang (1) (2) (6)
  Cheng Allen Chang (1) (6) (7)
  
  1. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Linong St., Beitou District, Taipei, 112, Taiwan, ROC
  2. Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, 112, Taiwan, ROC
  3. Department of Medical Research and Development, Chang Gung Memorial Hospital-Chiayi Branch, Chiayi, 613, Taiwan, ROC
  4. Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 112, Taiwan, ROC
  6. Biophotonics & Molecular Imaging Research Center, National Yang-Ming University, Taipei, 112, Taiwan, ROC
  5. Department of Oncology Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan, ROC
  7. Biomedical Engineering Research and Development Center, National Yang-Ming University, Taipei, 112, Taiwan, ROC
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Biomedicine
  
• 出版者：Springer Netherlands
• ISSN：1423-0127

文摘

Background The enzyme-prodrug system is considered a promising tool for tumor treatment when conjugated with a targeting molecule. The asparagine-glycine-arginine (NGR) motif is a developing and interesting targeting peptide that could specifically bind to aminopeptidase N (APN), which is an NGR receptor expressed on the cell membrane of angiogenic endothelial cells and a number of tumor cells within the tumor tissues. The objective of this study was to develop a novel targeted enzyme-prodrug system using 5-fluorocytosine (5-FC) and an NGR-containing peptide fused with yeast cytosine deaminase (yCD), i.e. CNGRC-yCD fusion protein, to target APN-expressing cells within the tumor tissues and to convert 5-FC into 5-fluorouracil (5-FU) to kill tumors.