Efficient expression of full-length antibodies in the cytoplasm of engineered bacteria

Nature Communications

Volumn 6, Issue , 2015, Pages

  Robinson, Michael Paul ^a   Ke, Na ^b   Lobstein, Julie ^b,c   Peterson, Cristen ^a   Szkodny, Alana ^a   Mansell, Thomas J ^a   Tuckey, Corinna ^b   Riggs, Paul D ^b   Colussi, Paul A ^b,d   Noren, Christopher J ^b   Taron, Christopher H ^b   Delisa, Matthew P ^a   Berkmen, Mehmet ^b  

^a School of Operations Research and Industrial Engineering   (United States)

^b NEW ENGLAND BIOLABS   (United States)

^c MOLECULAR PARTNERS AG   (Switzerland)

^d Tetragenetics Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FC RECEPTOR; IMMUNOGLOBULIN G ANTIBODY; PROSTATE SPECIFIC MEMBRANE ANTIGEN; RNA POLYMERASE; ANTIBODY; IMMUNOGLOBULIN G;

ANTIBODY; ANTIGEN; BACTERIUM; CRYSTALLIZATION; CYTOPLASM; GENE EXPRESSION; GENETIC ENGINEERING; METABOLISM; SECRETION;

AMINO ACID SUBSTITUTION; ANTIGEN BINDING; ARTICLE; BACTERIAL STRAIN; BIOENGINEERING; BIOSYNTHESIS; CRYSTALLIZATION; CYTOPLASM; DISULFIDE BOND; ENZYME LINKED IMMUNOSORBENT ASSAY; ESCHERICHIA COLI; GLYCOSYLATION; HUMAN; LIGHT CHAIN; MOUSE; NONHUMAN; PROTEIN FOLDING; SIZE EXCLUSION CHROMATOGRAPHY; WESTERN BLOTTING; ANTIBODY PRODUCTION; BACTERIOPHAGE; GENETICS; METABOLISM; PLASMID; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN TRANSPORT; SURFACE PLASMON RESONANCE; TRANSGENIC ORGANISM;

ESCHERICHIA COLI;

ANTIBODIES; ANTIBODY FORMATION; BACTERIOPHAGES; BLOTTING, WESTERN; CYTOPLASM; ELECTROPHORESIS, POLYACRYLAMIDE GEL; ENZYME-LINKED IMMUNOSORBENT ASSAY; ESCHERICHIA COLI; GLYCOSYLATION; IMMUNOGLOBULIN G; ORGANISMS, GENETICALLY MODIFIED; PLASMIDS; PROTEIN TRANSPORT; SURFACE PLASMON RESONANCE;

EID: 84940554764     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9072     Document Type: Article

References (52)

1. Reichert, J. M. Marketed therapeutic antibodies compendium. MAbs 4, 413-415 (2012).
2. Li, F., Vijayasankaran, N., Shen, A. Y., Kiss, R. & Amanullah, A. Cell culture processes for monoclonal antibody production. MAbs 2, 466-479 (2010).
3. Zhou, C., Jacobsen, F. W., Cai, L., Chen, Q. & Shen, W. D. Development of a novel mammalian cell surface antibody display platform. MAbs 2, 508-518 (2010).
4. Beerli, R. R. et al. Isolation of human monoclonal antibodies by mammalian cell display. Proc. Natl Acad. Sci. USA 105, 14336-14341 (2008).
5. Chartrain, M. & Chu, L. Development and production of commercial therapeutic monoclonal antibodies in Mammalian cell expression systems: an overview of the current upstream technologies. Curr. Pharm. Biotechnol. 9, 447-467 (2008).
6. Farid, S. S. Process economics of industrial monoclonal antibody manufacture. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 848, 8-18 (2007).
7. Yin, G. et al. Aglycosylated antibodies and antibody fragments produced in a scalable in vitro transcription-translation system. MAbs 4, 217-225 (2012).
8. Mayfield, S. P., Franklin, S. E. & Lerner, R. A. Expression and assembly of a fully active antibody in algae. Proc. Natl Acad. Sci. USA 100, 438-442 (2003).
9. Palmberger, D. et al. Insect cells for antibody production: evaluation of an efficient alternative. J. Biotechnol. 153, 160-166 (2011).
10. Orzaez, D., Granell, A. & Blazquez, M. A. Manufacturing antibodies in the plant cell. Biotechnol. J. 4, 1712-1724 (2009).
11. Johansson, D. X. et al. Efficient expression of recombinant human monoclonal antibodies in Drosophila S2 cells. J. Immunol. Methods 318, 37-46 (2007).
12. Kadokura, H., Katzen, F. & Beckwith, J. Protein disulfide bond formation in prokaryotes. Annu. Rev. Biochem. 72, 111-135 (2003).
13. Bessette, P. H., Aslund, F., Beckwith, J. & Georgiou, G. Efficient folding of proteins with multiple disulfide bonds in the Escherichia coli cytoplasm. Proc. Natl Acad. Sci. USA 96, 13703-13708 (1999).
14. Lobstein, J. et al. SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm. Microb. Cell Fact. 11, 56 (2012).
15. Shibui, T. & Nagahari, K. Secretion of a functional Fab fragment in Escherichia coli and the influence of culture conditions. Appl. Microbiol. Biotechnol. 37, 352-357 (1992).
16. Skerra, A., Pfitzinger, I. & Pluckthun, A. The functional expression of antibody Fv fragments in Escherichia coli: improved vectors and a generally applicable purification technique. Biotechnology 9, 273-278 (1991).
17. Jendeberg, L. et al. Engineering of Fc(1) and Fc(3) from human immunoglobulin G to analyse subclass specificity for staphylococcal protein A. J. Immunol. Methods 201, 25-34 (1997).
18. Sonoda, H., Kumada, Y., Katsuda, T. & Yamaji, H. Cytoplasmic production of soluble and functional single-chain Fv-Fc fusion protein in Escherichia coli. Biochem. Eng. J. 53, 253-259 (2011).
19. Jurado, P., Ritz, D., Beckwith, J., de Lorenzo, V. & Fernandez, L. A. Production of functional single-chain Fv antibodies in the cytoplasm of Escherichia coli. J. Mol. Biol. 320, 1-10 (2002).
20. Levy, R., Weiss, R., Chen, G., Iverson, B. L. & Georgiou, G. Production of correctly folded Fab antibody fragment in the cytoplasm of Escherichia coli trxB gor mutants via the coexpression of molecular chaperones. Protein Expr. Purif. 23, 338-347 (2001).
21. Venturi, M., Seifert, C. & Hunte, C. High level production of functional antibody Fab fragments in an oxidizing bacterial cytoplasm. J. Mol. Biol. 315, 1-8 (2002).
22. Mazor, Y., Van Blarcom, T., Mabry, R., Iverson, B. L. & Georgiou, G. Isolation of engineered, full-length antibodies from libraries expressed in Escherichia coli. Nat. Biotechnol. 25, 563-565 (2007).
23. Simmons, L. C. et al. Expression of full-length immunoglobulins in Escherichia coli: rapid and efficient production of aglycosylated antibodies. J. Immunol. Methods 263, 133-147 (2002).
24. Hakim, R. & Benhar, I. 'Inclonals': IgGs and IgG-enzyme fusion proteins produced in an E. coli expression-refolding system. MAbs 1, 281-287 (2009).
25. Cabilly, S. et al. Generation of antibody activity from immunoglobulin polypeptide chains produced in Escherichia coli. Proc. Natl Acad. Sci. USA 81, 3273-3277 (1984).
26. Boss, M. A., Kenten, J. H., Wood, C. R. & Emtage, J. S. Assembly of functional antibodies from immunoglobulin heavy and light chains synthesised in E. coli. Nucleic Acids Res. 12, 3791-3806 (1984).
27. Alder, N. N. & Theg, S. M. Energy use by biological protein transport pathways. Trends Biochem. Sci. 28, 442-451 (2003).
28. Stanley, N. R., Findlay, K., Berks, B. C. & Palmer, T. Escherichia coli strains blocked in Tat-dependent protein export exhibit pleiotropic defects in the cell envelope. J. Bacteriol. 183, 139-144 (2001).
29. Ravetch, J. V. & Bolland, S. IgG Fc receptors. Annu. Rev. Immunol. 19, 275-290 (2001).
30. Jefferis, R., Lund, J. & Pound, J. D. IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation. Immunol. Rev. 163, 59-76 (1998).
31. Jefferis, R. Recombinant antibody therapeutics: the impact of glycosylation on mechanisms of action. Trends Pharmacol. Sci. 30, 356-362 (2009).
32. Sazinsky, S. L. et al. Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors. Proc. Natl Acad. Sci. USA 105, 20167-20172 (2008).
33. Jung, S. T. et al. Aglycosylated IgG variants expressed in bacteria that selectively bind FcgammaRI potentiate tumor cell killing by monocyte-dendritic cells. Proc. Natl Acad. Sci. USA 107, 604-609 (2010).
34. Jung, S. T. et al. Effective phagocytosis of low Her2 tumor cell lines with engineered, aglycosylated IgG displaying high FcgammaRIIa affinity and selectivity. ACS Chem. Biol. 8, 368-375 (2012).
35. Braakman, I. & Bulleid, N. J. Protein folding and modification in the mammalian endoplasmic reticulum. Annu. Rev. Biochem. 80, 71-99 (2011).
36. Yuan, S. et al. The role of thioredoxin and disulfide isomerase in the expression of the snake venom thrombin-like enzyme calobin in Escherichia coli BL21 (DE3). Protein Expr. Purif. 38, 51-60 (2004).
37. Clark, M. Antibody humanization: a case of the 'Emperor's new clothes'? Immunol. Today 21, 397-402 (2000).
38. Boulianne, G. L., Hozumi, N. & Shulman, M. J. Production of functional chimaeric mouse/human antibody. Nature 312, 643-646 (1984).
39. Morrison, S. L., Johnson, M. J., Herzenberg, L. A. & Oi, V. T. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc. Natl Acad. Sci. USA 81, 6851-6855 (1984).
40. Carter, P. et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl Acad. Sci. USA 89, 4285-4289 (1992).
41. Koch, H., Grafe, N., Schiess, R. & Pluckthun, A. Direct selection of antibodies from complex libraries with the protein fragment complementation assay. J. Mol. Biol. 357, 427-441 (2006).
42. der Maur, A. A. et al. Direct in vivo screening of intrabody libraries constructed on a highly stable single-chain framework. J. Biol. Chem. 277, 45075-45085 (2002).
43. Jermutus, L., Honegger, A., Schwesinger, F., Hanes, J. & Pluckthun, A. Tailoring in vitro evolution for protein affinity or stability. Proc. Natl Acad. Sci. USA 98, 75-80 (2001).
44. Jefferis, R. Glycosylation of recombinant antibody therapeutics. Biotechnol. Prog. 21, 11-16 (2005).
45. Schaefer, J. V. & Pluckthun, A. Transfer of engineered biophysical properties between different antibody formats and expression systems. Protein Eng. Des. Sel. 25, 485-506 (2012).
46. van Stelten, J., Silva, F., Belin, D. & Silhavy, T. J. Effects of antibiotics and a proto-oncogene homolog on destruction of protein translocator SecY. Science 325, 753-756 (2009).
47. Chan, C. E., Lim, A. P., Chan, A. H., MacAry, P. A. & Hanson, B. J. Optimized expression of full-length IgG1 antibody in a common E. coli strain. PLoS ONE 5, e10261 (2010).
48. Makino, T., Skretas, G., Kang, T. H. & Georgiou, G. Comprehensive engineering of Escherichia coli for enhanced expression of IgG antibodies. Metab. Eng. 13, 241-251 (2011).
49. Skerra, A. & Pluckthun, A. Assembly of a functional immunoglobulin Fv fragment in Escherichia coli. Science 240, 1038-1041 (1988).
50. Better, M., Chang, C. P., Robinson, R. R. & Horwitz, A. H. Escherichia coli secretion of an active chimeric antibody fragment. Science 240, 1041-1043 (1988).
51. Kearney, J. F., Radbruch, A., Liesegang, B. & Rajewsky, K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J. Immunol. 123, 1548-1550 (1979).
52. Kabat, E. A., Te Wu, T., Gottesman, K. S. & Foeller, C. Sequences of Proteins of Immunological Interest. 1, 1571-1610 (Diane Publishing, 1992).