General strategy for the generation of human antibody variable domains with increased aggregation resistance

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 27, 2012, Pages 10879-10884

  Dudgeon, Kip ^a   Rouet, Romain ^a,b   Kokmeijer, Iris ^a   Schofield, Peter ^a   Stolp, Jessica ^a   Langley, David ^a,c   Stock, Daniela ^b,c   Christ, Daniel ^a,b  

^a GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

^c VICTOR CHANG CARDIAC RESEARCH INSTITUTE   (Australia)

Author keywords

Antibody therapeutics; Biotechnology; Monoclonal antibodies; Protein aggregation; Protein engineering

Indexed keywords

ASPARTIC ACID; GLUTAMIC ACID; TRASTUZUMAB;

ANTIBODY AGGREGATION RESISTANCE; ANTIBODY COMBINING SITE; ANTIBODY ENGINEERING; ANTIBODY STRUCTURE; ANTIGEN BINDING; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CRYSTAL STRUCTURE; GENE MUTATION; HEAVY CHAIN; LIGHT CHAIN; PHAGE DISPLAY; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FOLDING;

ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; BIOPHYSICS; BREAST NEOPLASMS; CRYSTALLOGRAPHY; DRUG DESIGN; FEMALE; HUMANS; IMMUNOGLOBULIN VARIABLE REGION; MUTATION; PEPTIDE LIBRARY; PROTEIN ENGINEERING;

EID: 84863570483     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1202866109     Document Type: Article

References (40)

1. Lowe D, et al. (2011) Aggregation, stability, and formulation of human antibody therapeutics. Adv Protein Chem Struct Biol 84:41-61.
2. Demarest SJ, Glaser SM (2008) Antibody therapeutics, antibody engineering, and the merits of protein stability. Curr Opin Drug Discov Devel 11:675-687.
3. Ewert S, Huber T, Honegger A, Pluckthun A (2003) Biophysical properties of human antibody variable domains. J Mol Biol 325:531-553. (Pubitemid 36062681)
4. Holliger P, Hudson PJ (2005) Engineered antibody fragments and the rise of single domains. Nat Biotechnol 23:1126-1136. (Pubitemid 41486394)
5. Hamers-Casterman C, et al. (1993) Naturally occurring antibodies devoid of light chains. Nature 363:446-448. (Pubitemid 23179389)
6. Ewert S, Cambillau C, Conrath K, Pluckthun A (2002) Biophysical properties of camelid V (HH) domains compared to those of human V (H)3 domains. Biochemistry 41:3628-3636. (Pubitemid 34224675)
7. Muyldermans S, Atarhouch T, Saldanha J, Barbosa JA, Hamers R (1994) Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains. Protein Eng 7:1129-1135. (Pubitemid 24282500)
8. Barthelemy PA, et al. (2008) Comprehensive analysis of the factors contributing to the stability and solubility of autonomous human VH domains. J Biol Chem 283:3639-3654.
9. Christ D, Dudgeon K (2011) Modified Variable Domain Molecules and Methods for Producing and Using Same. WO/2011/047442 (April 04, 2011).
10. Jespers L, Schon O, James LC, Veprintsev D, Winter G (2004) Crystal structure of HEL4 a soluble, refoldable human V(H) single domain with a germ-line scaffold. J Mol Biol 337:893-903. (Pubitemid 38368933)
11. Perchiacca JM, Bhattacharya M, Tessier PM (2011) Mutational analysis of domain antibodies reveals aggregation hotspots within and near the complementarity determining regions. Proteins 79:2637-2647.
12. Riechmann L (1996) Rearrangement of the former VL interface in the solution structure of a camelised, single antibody VH domain. J Mol Biol 259:957-969.
13. Cox JP, Tomlinson IM, Winter G (1994) A directory of human germ-line V kappa segments reveals a strong bias in their usage. Eur J Immunol 24:827-836.
14. Tomlinson IM, Walter G, Marks JD, Llewelyn MB, Winter G (1992) The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops. J Mol Biol 227:776-798.
15. Tomlinson IM, et al. (1996) The imprint of somatic hypermutation on the repertoire of human germline V genes. J Mol Biol 256:813-817. (Pubitemid 26108820)
16. Christ D, Famm K, Winter G (2006) Tapping diversity lost in transformations - In vitro amplification of ligation reactions. Nucleic Acids Res 34:e108.
17. Christ D, Famm K, Winter G (2007) Repertoires of aggregation-resistant human antibody domains. Protein Eng Des Sel 20:413-416. (Pubitemid 47428968)
18. Dudgeon K, Famm K, Christ D (2009) Sequence determinants of protein aggregation in human VH domains. Protein Eng Des Sel 22:217-220.
19. MacCallum RM, Martin AC, Thornton JM (1996) Antibody-antigen interactions: Contact analysis and binding site topography. J Mol Biol 262:732-745. (Pubitemid 26343518)
20. Jespers L, Schon O, Famm K, Winter G (2004) Aggregation-resistant domain antibodies selected on phage by heat denaturation. Nat Biotechnol 22:1161-1165. (Pubitemid 39166856)
21. Nelson AL, Dhimolea E, Reichert JM (2010) Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 9:767-774.
22. Jansson B, Uhlen M, Nygren PA (1998) All individual domains of staphylococcal protein A show Fab binding. FEMS Immunol Med Microbiol 20:69-78. (Pubitemid 28075421)
23. Knappik A, et al. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J Mol Biol 296:57-86.
24. Carter P, et al. (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 89:4285-4289.
25. Bostrom J, et al. (2009) Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323:1610-1614.
26. Lawrence MS, Phillips KJ, Liu DR (2007) Supercharging proteins can impart unusual resilience. J Am Chem Soc 129:10110-10112. (Pubitemid 47312950)
27. Suzuki I, Pfister L, Glas A, Nottenburg C, Milner EC (1995) Representation of rearranged VH gene segments in the human adult antibody repertoire. J Immunol 154:3902-3911.
28. Foster SJ, Brezinschek HP, Brezinschek RI, Lipsky PE (1997) Molecular mechanisms and selective influences that shape the kappa gene repertoire of IgM+ B cells. J Clin Invest 99:1614-1627. (Pubitemid 27163812)
29. Virnekas B, et al. (1994) Trinucleotide phosphoramidites: Ideal reagents for the synthesis of mixed oligonucleotides for random mutagenesis. Nucleic Acids Res 22:5600-5607.
30. Kabat E, Wu TT, Perry HM, Kay S, Gottesman CF (1992) Sequences of Proteins of Immunological Interest (Diane Publishing, Darby, PA), 5th Ed, p 2719.
31. Wang X, Das TK, Singh SK, Kumar S (2009) Potential aggregation prone regions in biotherapeutics: A survey of commercial monoclonal antibodies. MAbs 1:254-267.
32. Ewert S, Honegger A, Pluckthun A (2003) Structure-based improvement of the biophysical properties of immunoglobulin VH domains with a generalizable approach. Biochemistry 42:1517-1528. (Pubitemid 36205958)
33. Chiti F, Stefani M, Taddei N, Ramponi G, Dobson CM (2003) Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature 424:805-808. (Pubitemid 37021713)
34. Jones PT, Dear PH, Foote J, Neuberger MS, Winter G (1986) Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321:522-525. (Pubitemid 16052256)
35. Kelley RF, O'Connell MP (1993) Thermodynamic analysis of an antibody functional epitope. Biochemistry 32:6828-6835. (Pubitemid 23221612)
36. Cho HS, et al. (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421:756-760.
37. Schaefer JV, Pluckthun A (2012) Engineering aggregation resistance in IgG by two independent mechanisms: Lessons from comparison of Pichia pastoris and mammalian cell expression. J Mol Biol 417:309-335.
38. Reichert JM, Rosensweig CJ, Faden LB, Dewitz MC (2005) Monoclonal antibody successes in the clinic. Nat Biotechnol 23:1073-1078. (Pubitemid 41486385)
39. Hwang WY, Foote J (2005) Immunogenicity of engineered antibodies. Methods 36:3-10. (Pubitemid 40558811)
40. Chothia C, Lesk AM (1987) Canonical structures for the hypervariable regions of immunoglobulins. J Mol Biol 196:901-917. (Pubitemid 17127946)