Engineering an aglycosylated Fc variant for enhanced FcγRI engagement and pH-dependent human FcRn binding

Biotechnology and Bioprocess Engineering

Volumn 19, Issue 5, 2014, Pages 780-789

  Jung, Sang Taek ^a   Kang, Tae Hyun ^b   Kim, Dong il ^c  

^a Kookmin University   (South Korea)

^b The University of Texas at Austin   (United States)

^c Inha University   (South Korea)

Author keywords

antibody Fc; directed evolution; effector functions; Fc RI (CD64); neonatal Fc receptor (FcRn)

Indexed keywords

BACTERIA; BINDING ENERGY; CELLS; CHEMICAL ACTIVATION; DIAGNOSIS; MAMMALS; MONOCLONAL ANTIBODIES;

BINDING AFFINITIES; COMBINATORIAL LIBRARY; DIRECTED EVOLUTION; IMMUNE EFFECTOR CELLS; LIBRARY SCREENING; NEONATAL FC RECEPTORS; SMALL-MOLECULE DRUGS; THERAPEUTIC ANTIBODIES;

CYTOLOGY;

AGLYCOSYLATED IMMUNOGLOBULIN FC FRAGMENT; AGLYCOSYLATED IMMUNOGLOBULIN FC FRAGMENT 5; AGLYCOSYLATED IMMUNOGLOBULIN FC FRAGMENT 701; FC RECEPTOR; FC RECEPTOR I; IMMUNOGLOBULIN FC FRAGMENT; TRASTUZUMAB; UNCLASSIFIED DRUG;

ANTIBODY ENGINEERING; ANTIBODY SPECIFICITY; ARTICLE; BINDING AFFINITY; COMBINATORIAL LIBRARY; CONTROLLED STUDY; DRUG RECEPTOR BINDING; ESCHERICHIA COLI; FED BATCH FERMENTATION; FLOW CYTOMETRY; HIGH THROUGHPUT SCREENING; NONHUMAN; PH; PROTEIN DOMAIN; SURFACE PLASMON RESONANCE; WILD TYPE;

EID: 84904364868     PISSN: 12268372     EISSN: 19763816     Source Type: Journal    
DOI: 10.1007/s12257-013-0432-z     Document Type: Article

References (38)

1. Reichert, J. M. (2012) Marketed therapeutic antibodies compendium. MAbs. 4: 413–415.
2. Ryu, J., H. Kim, and D. Nam (2012) Current status and perspectives of biopharmaceutical drugs. Biotechnol. Bioproc. Eng. 17: 900–911.
3. Hogarth, P. M. and G. A. Pietersz (2012) Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond. Nat. Rev. Drug Discov. 11: 311–331.
4. Jung, S. (2013) Tailoring immunoglobulin Fc for highly potent and serum-stable therapeutic antibodies. Biotechnol. Bioproc. Eng. 18: 625–636.
5. Jung, S. T., T. H. Kang, and G. Georgiou (2010) Efficient expression and purification of human aglycosylated Fcγ receptors in Escherichia coli. Biotechnol. Bioeng. 107: 21–30.
6. Nimmerjahn, F. and J. V. Ravetch (2008) Fcγ receptors as regulators of immune responses. Nat. Rev. Immunol. 8: 34–47.
7. Jung, S. T., S. T. Reddy, T. H. Kang, M. J. Borrok, I. Sandlie, P. W. Tucker, and G. Georgiou (2010) Aglycosylated IgG variants expressed in bacteria that selectively bind FcγRI potentiate tumor cell killing by monocyte-dendritic cells. Proc. Natl. Acad. Sci. USA. 107: 604–609.
8. Bruhns, P., B. Iannascoli, P. England, D. A. Mancardi, N. Fernandez, S. Jorieux, and M. Daëron (2009) Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses. Blood 113: 3716–3725.
9. Lu, J., J. L. Ellsworth, N. Hamacher, S. W. Oak, and P. D. Sun (2011) Crystal structure of Fcγ receptor I and its implication in high affinity γ-immunoglobulin binding. J. Biol. Chem. 286: 40608–40613.
10. Pfefferkorn, L. C. and M. W. Fanger (1989) Cross-linking of the high affinity Fc receptor for human immunoglobulin G1 triggers transient activation of NADPH oxidase activity. Continuous oxidase activation requires continuous de novo receptor cross-linking. J. Biol. Chem. 264: 14112–14120.
11. Bevaart, L., J. Goldstein, L. Vitale, C. Russoniello, J. Treml, J. Zhang, R. F. Graziano, J. H. W. Leusen, J. G. J. Winkel, and T. Keler (2006) Direct targeting of genetically modified tumour cells to FcγRI triggers potent tumour cytotoxicity. Brit. J. Haematol. 132: 317–325.
12. van der Poel, C. E., R. M. Spaapen, J. G. van de Winkel, and J. H. Leusen (2011) Functional characteristics of the high affinity IgG receptor, FcγRI. J. Immunol. 186: 2699–2704.
13. Cohen-Solal, J. F., L. Cassard, W. H. Fridman, and C. Sautes-Fridman (2004) Fc gamma receptors. Immunol. Lett. 92: 199–205.
14. Yeung, Y. A., M. K. Leabman, J. S. Marvin, J. Qiu, C. W. Adams, S. Lien, M. A. Starovasnik, and H. B. Lowman (2009) Engineering human IgG1 affinity to human neonatal Fc receptor: Impact of affinity improvement on pharmacokinetics in primates. J. Immunol. 182: 7663–7671.
15. Kuo, T. T. and V. G. Aveson (2011) Neonatal Fc receptor and IgG-based therapeutics. MAbs. 3: 422–430.
16. Roopenian, D. C. and S. Akilesh (2007) FcRn: The neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7: 715–725.
17. Valdés, R., A. Tamayo, M. González, S. Padilla, D. Geada, W. Ferro, L. Milá, L. Gómez, R. Alemán, A. Leyva, C. García, O. Mendoza, T. Alvarez, L. Dorta, Y. Villega, D. Cecilia, H. Aragón, T. González, M. La O, and J. López (2012) Production of a monoclonal antibody by ascites, hollow fiber system, and transgenic plants for vaccine production using CB.Hep-1 mAb as a study case. Biotechnol. Bioproc. Eng. 17: 145–159.
18. Du, Z., M. Mujacic, K. Le, G. Caspary, H. Nunn, C. Heath, and P. Reddy (2013) Analysis of heterogeneity and instability of stable mAb-expressing CHO cells. Biotechnol. Bioproc. Eng. 18: 419–429.
19. Chames, P., M. V. Regenmortel, E. Weiss, and D. Baty (2009) Therapeutic antibodies: Successes, limitations and hopes for the future. Brit. J. Pharmacol. 157: 220–233.
20. Simmons, L. C., D. Reilly, L. Klimowski, T. S. Raju, G. Meng, P. Sims, K. Hong, R. L. Shields, L. A. Damico, P. Rancatore, and D. G. Yansura (2002) Expression of full-length immunoglobulins in Escherichia coli: Rapid and efficient production of aglycosylated antibodies. J. Immunol. Methods. 263: 133–147.
21. Kipriyanov, S. M. and M. Little (1999) Generation of recombinant antibodies. Mol. Biotechnol. 12: 173–201.
22. Jeong, K. J., S. H. Jang, and N. Velmurugan (2011) Recombinant antibodies: Engineering and production in yeast and bacterial hosts. Biotechnol. J. 6: 16–27.
23. Lee, Y. J., H. S. Kim, A. J. Ryu, and K. J. Jeong (2013) Enhanced production of full-length immunoglobulin G via the signal recognition particle (SRP)-dependent pathway in Escherichia coli. J. Biotechnol. 165: 102–108.
24. Borrok, M. J., S. T. Jung, T. H. Kang, A. F. Monzingo, and G. Georgiou (2012) Revisiting the role of glycosylation in the structure of human IgG Fc. ACS Chem. Biol. 7: 1596–1602.
25. Jung, S. T., W. Kelton, T. H. Kang, D. T. W. Ng, J. T. Andersen, I. Sandlie, C. A. Sarkar, and G. Georgiou (2012) Effective phagocytosis of low Her2 tumor cell lines with engineered, aglycosylated IgG displaying high FcγRIIa affinity and selectivity. ACS Chem. Biol. 8: 368–375.
26. Berntzen, G., E. Lunde, M. Flobakk, J. T. Andersen, V. Lauvrak, and I. Sandlie (2005) Prolonged and increased expression of soluble Fc receptors, IgG and a TCR-Ig fusion protein by transiently transfected adherent 293E cells. J. Immunol. Methods. 298: 93–104.
27. Kabat, E. A., T. T. Wu, H. M. Perry, K. S. Gottesman, and C. Foeller (1991) Sequences of Proteins of Immunological Interest. U.S. Dept. of Health and Hum. Serv., Bethesda.
28. Kawarasaki, Y., K. E. Griswold, J. D. Stevenson, T. Selzer, S. J. Benkovic, B. L. Iverson, and G. Georgiou (2003) Enhanced crossover SCRATCHY: Construction and high-throughput screening of a combinatorial library containing multiple nonhomologous crossovers. Nucleic Acids Res. 31: e126.
29. Andersen, J. T., J. Dee Qian, and I. Sandlie (2006) The conserved histidine 166 residue of the human neonatal Fc receptor heavy chain is critical for the pH-dependent binding to albumin. Eur. J. Immunol. 36: 3044–3051.
30. Jung, S. T., T. H. Kang, W. Kelton, and G. Georgiou (2011) Bypassing glycosylation: Engineering aglycosylated full-length IgG antibodies for human therapy. Curr. Opin. Biotechnol. 22: 858–867.
31. Raghavan, M. and P. J. Bjorkman (1996) Fc receptors and their interactions with immunoglobulins. Annu. Rev. Cell Dev. Biol. 12: 181–220.
32. Ober, R. J., C. Martinez, X. Lai, J. Zhou, and E. S. Ward (2004) Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level. Proc. Natl. Acad. Sci. USA. 101: 11076-110–1.
33. Dall’Acqua, W. F., P. A. Kiener, and H. Wu (2006) Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J. Biol. Chem. 281: 23514–23524.
34. Sazinsky, S. L., R. G. Ott, N. W. Silver, B. Tidor, J. V. Ravetch, and K. D. Wittrup (2008) Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors. Proc. Natl. Acad. Sci. USA. 105: 20167–20172.
35. Kalergis, A. M. and J. V. Ravetch (2002) Inducing tumor immunity through the selective engagement of activating Fcγ receptors on dendritic cells. J. Exp. Med. 195: 1653–1659.
36. Boruchov, A. M., G. Heller, M.-C. Veri, E. Bonvini, J. V. Ravetch, and J. W. Young (2005) Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J. Clin. Invest. 115: 2914–2923.
37. Smith, P., D. J. DiLillo, S. Bournazos, F. Li, and J. V. Ravetch (2012) Mouse model recapitulating human Fcγ receptor structural and functional diversity. Proc. Natl. Acad. Sci. USA. 109: 6181–6186.
38. Roopenian, D. C., G. J. Christianson, and T. J. Sproule (2010) Human FcRn transgenic mice for pharmacokinetic evaluation of therapeutic antibodies. Methods Mol. Biol. 602: 93–104.