Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG

Nature Communications

Volumn 6, Issue , 2015, Pages

  Fischer, Nicolas ^a   Elson, Greg ^a,b   Magistrelli, Giovanni ^a   Dheilly, Elie ^a   Fouque, Nicolas ^a   Laurendon, Amélie ^a,b   Gueneau, Franck ^a   Ravn, Ulla ^a   Depoisier, Jean François ^a   Moine, Valery ^a   Raimondi, Sylvain ^a   Malinge, Pauline ^a   Di Grazia, Laura ^a   Rousseau, François ^a   Poitevin, Yves ^a   Calloud, Sébastien ^a   Cayatte, Pierre Alexis ^a   Alcoz, Mathias ^a   Pontini, Guillemette ^a   Fagète, Séverine ^a,c   Broyer, Lucile ^a   Corbier, Marie ^a   Schrag, Delphine ^a   Didelot, Gérard ^a   Bosson, Nicolas ^a   Costes, Nessie ^a   Cons, Laura ^a   Buatois, Vanessa ^a   Johnson, Zoe ^a   Ferlin, Walter ^a   Masternak, Krzysztof ^a   Kosco Vilbois, Marie ^a   more..

^a NOVIMMUNE SA   (Switzerland)

^b Glenmark Pharmaceuticals S A   (Switzerland)

^c UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN G; IMMUNOGLOBULIN KAPPA CHAIN; IMMUNOGLOBULIN LAMBDA CHAIN; MONOCLONAL ANTIBODY; BISPECIFIC ANTIBODY; IMMUNOGLOBULIN HEAVY CHAIN; IMMUNOGLOBULIN LIGHT CHAIN; PEPTIDE LIBRARY;

ANTIBODY; DOMINANCE; DRUG; GENE EXPRESSION; HUMAN GEOGRAPHY;

ANTIGEN BINDING; ARTICLE; CONTROLLED STUDY; DOWNSTREAM PROCESSING; HEAVY CHAIN; HUMAN; IN VITRO STUDY; LIGHT CHAIN; PURIFICATION; T LYMPHOCYTE; TARGET CELL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOLOGY; ISOLATION AND PURIFICATION; METABOLISM; PEPTIDE LIBRARY; PROCEDURES; PROTEIN ENGINEERING; SERODIAGNOSIS;

ANTIBODIES, BISPECIFIC; ANTIBODIES, MONOCLONAL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; HUMANS; IMMUNOGLOBULIN G; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN KAPPA-CHAINS; IMMUNOGLOBULIN LIGHT CHAINS; NEUTRALIZATION TESTS; PEPTIDE LIBRARY; PROTEIN ENGINEERING; T-LYMPHOCYTES;

EID: 84923247651     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms7113     Document Type: Article

References (44)

1. Reichert, J. M. Marketed therapeutic antibodies compendium. MAbs 4, 413 (2012).
2. Frankel, S. R. & Baeuerle, P. A. Targeting T cells to tumor cells using bispecific antibodies. Curr. Opin. Chem. Biol. 17, 385 (2013).
3. Kitazawa, T. et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat. Med. 18, 1570 (2012).
4. Watts, R. J. & Dennis, M. S. Bispecific antibodies for delivery into the brain. Curr. Opin. Chem. Biol. 17, 393 (2013).
5. Weidle, U. H. et al. The intriguing options of multispecific antibody formats for treatment of cancer. Cancer Genomics Proteomics 10, 1 (2013).
6. Bargou, R. et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 321, 974 (2008).
7. Portell, C. A., Wenzell, C. M. & Advani, A. S. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin. Pharmacol. 5(Suppl 1): 5 (2013).
8. Seimetz, D., Lindhofer, H. & Bokemeyer, C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat. Rev. 36, 458 (2010).
9. Klein, C. et al. Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies. MAbs 4, 653 (2012).
10. Kontermann, R. Dual targeting strategies with bispecific antibodies. MAbs 4, 182 (2012).
11. Labrijn, A. F. et al. Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proc. Natl Acad. Sci. USA 110, 5145 (2013).
12. Ridgway, J. B., Presta, L. G. & Carter, P. Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng. 9, 617 (1996).
13. Wozniak-Knopp, G. et al. Introducing antigen-binding sites in structural loops of immunoglobulin constant domains: Fc fragments with engineered HER2/neu-binding sites and antibody properties. Protein Eng. Des. Sel. 23, 289 (2010).
14. Fischer, N. & Leger, O. Bispecific antibodies: molecules that enable novel therapeutic strategies. Pathobiology 74, 3 (2007).
15. Lewis, S. M. et al. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat. Biotechnol. 32, 191 (2014).
16. Müller-Späth, T. et al. Purifying common light-chain bispecific antibodies BioProcess International 11, 36 (2013).
17. Lefranc, M. P. et al. IMGT, the International ImMunoGeneTics database. Nucleic Acids Res. 26, 297 (1998).
18. Ewert, S. et al. Biophysical properties of human antibody variable domains. J. Mol. Biol. 325, 531 (2003).
19. Lloyd, C. et al. Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens. Protein Eng. Des. Sel. 22, 159 (2009).
20. Knappik, A. et al. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J. Mol. Biol. 296, 57 (2000).
21. Vaughan, T. J. et al. Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat. Biotechnol. 14, 309 (1996).
22. Chao, M. P., Weissman, I. L. & Majeti, R. The CD47-SIRPalpha pathway in cancer immune evasion and potential therapeutic implications. Curr. Opin. Immunol. 24, 225 (2012).
23. Murata, Y. et al. The CD47-SIRPalpha signalling system: its physiological roles and therapeutic application. J. Biochem. 155, 335 (2014).
24. Chao, M. P. et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell 142, 699 (2010).
25. Chen, S. H. et al. Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation. Sci. Rep. 3, 1870 (2013).
26. Bluemel, C. et al. Epitope distance to the target cell membrane and antigen size determine the potency of T cell-mediated lysis by BiTE antibodies specific for a large melanoma surface antigen. Cancer Immunol. Immunother. 59, 1197 (2010).
27. Haas, C. et al. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology 214, 441 (2009).
28. Schaefer, J. V. & Plückthun, A. Transfer of engineered biophysical properties between different antibody formats and expression systems. Protein Eng. Des. Sel. 25, 485 (2012).
29. Lin, Y. S. et al. Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor. J. Pharmacol. Exp. Ther. 288, 371 (1999).
30. Persson, H. et al. CDR-H3 diversity is not required for antigen recognition by synthetic antibodies. J. Mol. Biol. 425, 803 (2013).
31. Binz, H. K., Amstutz, P. & Plückthun, A. Engineering novel binding proteins from nonimmunoglobulin domains. Nat. Biotechnol. 23, 1257 (2005).
32. Hamers-Casterman, C. et al. Naturally occurring antibodies devoid of light chains. Nature 363, 446 (1993).
33. Ward, E. S. et al. Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature 341, 544 (1989).
34. Wang, F. et al. Reshaping antibody diversity. cell 153, 1379 (2013).
35. Spiess, C. et al. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat. Biotechnol. 31, 753 (2013).
36. Garber, K. Bispecific antibodies rise again. Nat. Rev. Drug Discov. 13, 799 (2014).
37. May, C., Sapra, P. & Gerber, H. P. Advances in bispecific biotherapeutics for the treatment of cancer. Biochem. Pharmacol. 84, 1105 (2012).
38. Rouet, R. & Christ, D. Bispecific antibodies with native chain structure. Nat. Biotechnol. 32, 136 (2014).
39. Hwang, W. Y. & Foote, J. Immunogenicity of engineered antibodies. Methods 36, 3 (2005).
40. Rombach-Riegraf, V. et al. Aggregation of human recombinant monoclonal antibodies influences the capacity of dendritic cells to stimulate adaptive T-cell responses in vitro. PLoS ONE 9 e86322 (2014).
41. Rosenberg, A. S. Effects of protein aggregates: an immunologic perspective. AAPS J 8, E501-E507 (2006).
42. Bostrom, J. et al. Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610 (2009).
43. Ravn, U. et al. By-passing in vitro screening-next generation sequencing technologies applied to antibody display and in silico candidate selection. Nucleic Acids Res. 38, e193 (2010).
44. Magistrelli, G. et al. Rapid, simple and high yield production of recombinant proteins in mammalian cells using a versatile episomal system. Protein Expr. Purif. 72, 209 (2010).