Journal of Microbiology and Biotechnology

  • 제23권9호
  • /
  • Pages.1327-1338
  • /
  • 2013
  • /
  • 1017-7825(pISSN)
  • /
  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
권호 표지
DOI QR코드

DOI QR Code

Inhibition of Tumor Growth in a Mouse Xenograft Model by the Humanized Anti-HGF Monoclonal Antibody YYB-101 Produced in a Large-Scale CHO Cell Culture

  • 투고 : 2013.06.07
  • 심사 : 2013.07.08
  • 발행 : 2013.09.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The humanized anti-hepatocyte growth factor (HGF) monoclonal antibody (mAb) YYB-101 is a promising therapeutic candidate for treating various cancers. In this study, we developed a bioprocess for large-scale production of YYB-101 and evaluated its therapeutic potential for tumor treatment using a xenograft mouse model. By screening diverse chemically defined basal media formulations and by assessing the effects of various feed supplements and feeding schedules on cell growth and antibody production, we established an optimal medium and feeding method to produce 757 mg/l of YYB-101 in flask cultures, representing a 7.5-fold increase in titer compared with that obtained under non-optimized conditions. The optimal dissolved oxygen concentration for antibody production was 70% $pO_2$. A pH shift from 7.2 to 7.0, rather than controlled pH of either 7.0 or 7.2, resulted in productivity improvement in 5 L and 200 L bioreactors, yielding 737 and 830 mg/ml of YYB-101, respectively. The YYB-101 mAb highly purified by affinity chromatography using a Protein A column and two-step ion exchange chromatography effectively neutralized HGF in a cell-based assay and showed potent tumor suppression activity in a mouse xenograft model established with human glioblastoma cells.

키워드

참고문헌

  1. Borset M, Waage A, Sundan A. 1996. Hepatocyte growth factor reverses the TGF-beta-induced growth inhibition of CCL-64 cells. A novel bioassay for HGF and implications for the TGF-beta bioassay. J. Immunol. Methods 189: 59-64. https://doi.org/10.1016/0022-1759(95)00228-6
  2. Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, et al. 1991. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251: 802-804. https://doi.org/10.1126/science.1846706
  3. Burgess T, Coxon A, Meyer S, Sun J, Rex K, Tsuruda T, et al. 2006. Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors. Cancer Res. 66: 1721-1729. https://doi.org/10.1158/0008-5472.CAN-05-3329
  4. Butler M. 2005. Animal cell cultures: recent achievements and perspectives in the production of biopharmaceuticals. Appl. Microbiol. Biotechnol. 68: 283-291. https://doi.org/10.1007/s00253-005-1980-8
  5. Cao B, Su Y, Oskarsson M, Zhao P, Kort EJ, Fisher RJ, et al. 2001. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc. Natl. Acad. Sci. USA 98: 7443-7448. https://doi.org/10.1073/pnas.131200498
  6. Cherrington JM, Strawn LM, Shawver LK. 2000. New paradigms for the treatment of cancer: the role of antiangiogenesis agents. Adv. Cancer Res. 79: 1-38. https://doi.org/10.1016/S0065-230X(00)79001-4
  7. Comoglio PM, Giordano S, Trusolino L. 2008. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat. Rev. Drug Discov. 7: 504-516. https://doi.org/10.1038/nrd2530
  8. Franek F, Hohenwarter O, Katinger H. 2000. Plant protein hydrolysates: preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol. Prog. 16: 688-692. https://doi.org/10.1021/bp0001011
  9. Gawlitzek M, Estacio M, Furch T, Kiss R. 2009. Identification of cell culture conditions to control N-glycosylation siteoccupancy of recombinant glycoproteins expressed in CHO cells. Biotechnol. Bioeng. 103: 1164-1175. https://doi.org/10.1002/bit.22348
  10. Giordano S. 2009. Rilotumumab, a mAb against human hepatocyte growth factor for the treatment of cancer. Curr. Opin. Mol. Ther. 11: 448-455.
  11. Heidemann R, Zhang C, Qi H, Larrick Rule J, Rozales C, Park S, et al. 2000. The use of peptones as medium additives for the production of a recombinant therapeutic protein in high density perfusion cultures of mammalian cells. Cytotechnology 32: 157-167. https://doi.org/10.1023/A:1008196521213
  12. Higuchi O, Mizuno K, Vande Woude GF, Nakamura T. 1992. Expression of c-met proto-oncogene in COS cells induces the signal transducing high-affinity receptor for hepatocyte growth factor. FEBS Lett. 301: 282-286. https://doi.org/10.1016/0014-5793(92)80257-H
  13. Jiang WG, Martin TA, Parr C, Davies G, Matsumoto K, Nakamura T. 2005. Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. Crit. Rev. Oncol. Hematol. 53: 35-69. https://doi.org/10.1016/j.critrevonc.2004.09.004
  14. Jin H, Yang R, Zheng Z, Romero M, Ross J, Bou-Reslan H, et al. 2008. MetMAb, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Res. 68: 4360-4368. https://doi.org/10.1158/0008-5472.CAN-07-5960
  15. Kim K, Hur Y, Ryu EK, Rhim JH, Choi CY, Baek CM, et al. 2007. A neutralizable epitope is induced on HGF upon its interaction with its receptor cMet. Biochem. Biophys. Res. Commun. 354: 115-121. https://doi.org/10.1016/j.bbrc.2006.12.164
  16. Kim KJ, Wang L, Su YC, Gillespie GY, Salhotra A, Lal B, et al. 2006. Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts. Clin. Cancer Res. 12: 1292-1298. https://doi.org/10.1158/1078-0432.CCR-05-1793
  17. Kuba K, Matsumoto K, Date K, Shimura H, Tanaka M, Nakamura T. 2000. HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice. Cancer Res. 60: 6737-6743.
  18. Kunkel JP, Jan DC, Jamieson JC, Butler M. 1998. Dissolved oxygen concentration in serum-free continuous culture affects N-linked glycosylation of a monoclonal antibody. J. Biotechnol. 62: 55-71. https://doi.org/10.1016/S0168-1656(98)00044-3
  19. Martens T, Schmidt NO, Eckerich C, Fillbrandt R, Merchant M, Schwall R, et al. 2006. A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin. Cancer Res. 12: 6144-6152. https://doi.org/10.1158/1078-0432.CCR-05-1418
  20. Matsumoto K, Nakamura T, Kramer RH. 1994. Hepatocyte growth factor/scatter factor induces tyrosine phosphorylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells. J. Biol. Chem. 269: 31807-31813.
  21. Miller WM, Wilke CR, Blanch HW. 1987. Effects of dissolved oxygen concentration on hybridoma growth and metabolism in continuous culture. J. Cell. Physiol. 132: 524-530. https://doi.org/10.1002/jcp.1041320315
  22. Munshi N, Jeay S, Li Y, Chen CR, France DS, Ashwell MA, et al. 2010. ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity. Mol. Cancer Ther. 9: 1544-1553. https://doi.org/10.1158/1535-7163.MCT-09-1173
  23. Nakamura T, Matsumoto K, Kiritoshi A, Tano Y. 1997. Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions. Cancer Res. 57: 3305-3313.
  24. Nakamura T, Nawa K, Ichihara A. 1984. Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem. Biophys. Res. Commun. 122: 1450-1459. https://doi.org/10.1016/0006-291X(84)91253-1
  25. Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, et al. 1989. Molecular cloning and expression of human hepatocyte growth factor. Nature 342: 440-443. https://doi.org/10.1038/342440a0
  26. Ozturk SS and Palsson BO. 1990. Effects of dissolved oxygen on hybridoma cell growth, metabolism, and antibody production kinetics in continuous culture. Biotechnol. Prog. 6: 437-446. https://doi.org/10.1021/bp00006a006
  27. Pinski J, Schally AV, Halmos G, Szepeshazi K, Groot K. 1994. Somatostatin analogues and bombesin/gastrin-releasing peptide antagonist RC-3095 inhibit the growth of human glioblastomas in vitro and in vivo. Cancer Res. 54: 5895-5901.
  28. Qian F, Engst S, Yamaguchi K, Yu P, Won KA, Mock L, et al. 2009. Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases. Cancer Res. 69: 8009-8016. https://doi.org/10.1158/0008-5472.CAN-08-4889
  29. Rafferty B, Maile P, Rigsby P, Gaines Das RE, Robinson CJ. 2001. International standards for hepatocyte growth factor/scatter factor: initial assessment of candidate materials and their evaluation by multicentre collaborative study. J. Immunol. Methods 258: 1-11. https://doi.org/10.1016/S0022-1759(01)00482-3
  30. Renard JM, Spagnoli R, Mazier C, Salles MF, Mandine E. 1988. Evidence that monoclonal antibody production kinetics is related to the integral of the viable cells in batch systems. Biotechnol. Lett. 10: 91-96. https://doi.org/10.1007/BF01024632
  31. Rosen EM, Laterra J, Joseph A, Jin L, Fuchs A, Way D, et al. 1996. Scatter factor expression and regulation in human glial tumors. Int. J. Cancer 67: 248-255. https://doi.org/10.1002/(SICI)1097-0215(19960717)67:2<248::AID-IJC16>3.0.CO;2-7
  32. Rubin JS, Bottaro DP, Aaronson SA. 1993. Hepatocyte growth factor/scatter factor and its receptor, the c-met proto-oncogene product. Biochim. Biophys. Acta 1155: 357-371.
  33. Schmid G, Blanch HW. Wilke CR. 1990. Hybridoma growth, metabolism, and product formation in HEPES-buffered medium: II. Effect of pH. Biotechnol. Lett. 12: 633-638. https://doi.org/10.1007/BF01088185
  34. Tsarfaty I, Rong S, Resau JH, Rulong S, da Silva PP, Vande Woude GF. 1994. The Met proto-oncogene mesenchymal to epithelial cell conversion. Science 263: 98-101. https://doi.org/10.1126/science.7505952
  35. Walsh G, Jefferis R. 2006. Post-translational modifications in the context of therapeutic proteins. Nat. Biotechnol. 24: 1241-1252. https://doi.org/10.1038/nbt1252

피인용 문헌

  1. Interaction of Stomatin with Hepatitis C Virus RNA Polymerase Stabilizes the Viral RNA Replicase Complexes on Detergent-Resistant Membranes vol.24, pp.12, 2013, https://doi.org/10.4014/jmb.1409.09063
  2. From rabbit antibody repertoires to rabbit monoclonal antibodies vol.49, pp.3, 2013, https://doi.org/10.1038/emm.2017.23
  3. Identification of genomic and molecular traits that present therapeutic vulnerability to HGF-targeted therapy in glioblastoma vol.21, pp.2, 2013, https://doi.org/10.1093/neuonc/noy105