Shark variable new antigen receptor biologics-A novel technology platform for therapeutic drug development

Expert Opinion on Biological Therapy

Volumn 14, Issue 10, 2014, Pages 1527-1539

  Kovaleva, Marina ^a   Ferguson, Laura ^a   Steven, John ^a   Porter, Andrew ^a   Barelle, Caroline ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

Author keywords

Binding domains; Biologics; Drug development; MAb; Novel scaffolds; Shark; Variable new antigen receptor

Indexed keywords

BIOLOGICAL PRODUCT; DRUG ANTIBODY; NANOBODY; UNCLASSIFIED DRUG; VARIABLE NEW ANTIGEN RECEPTOR; FISH PROTEIN; IMMUNOGLOBULIN VARIABLE REGION; LYMPHOCYTE ANTIGEN RECEPTOR;

ANTIBODY AFFINITY; ANTIBODY ENGINEERING; ANTIGEN BINDING; ANTIGEN SPECIFICITY; ARTICLE; BIOLOGICAL ACTIVITY; CLINICAL EVALUATION; DRUG DEVELOPMENT; DRUG INDICATION; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; HUMAN; MEDICAL TECHNOLOGY; NONHUMAN; ANIMAL; IMMUNOGLOBULIN VARIABLE REGION; IMMUNOLOGY; SHARK;

CHONDRICHTHYES;

ANIMALS; BIOLOGICAL PRODUCTS; DRUG DISCOVERY; FISH PROTEINS; HUMANS; IMMUNOGLOBULIN VARIABLE REGION; RECEPTORS, ANTIGEN; SHARKS;

EID: 84907056407     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1517/14712598.2014.937701     Document Type: Article

References (107)

1. Cohen SN, Chang AC, Boye r HW, Helling RB. Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA 1973;70:3240-4
2. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256:495-7
3. Wallace RB, Schold M, Johnson MJ, et al. Oligonucleotide directed mutagenesis of the human beta-globin gene: a general method for pro ducing specific point mutations in cloned DNA. Nucleic Acids Res 1981;9:3647-56
4. Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 1985;228:1315-17
5. McCafferty J, Griffiths AD, Winter G, Chiswell DJ. Phage antibodies: filamentous phage displaying antibody variable domains. Nature 1990;348:552-4
6. Bass S, Greene R, Wells JA. Hormone phage: an enrichment method for variant proteins with altered binding properties. Proteins 1990;8:309-14
7. Choo Y, Klug A. Toward a co de for the interactions of zinc fingers with DNA: selection of randomized fingers displayed on phage. Proc Natl Acad Sci USA 1994;91:11163-7
8. Hiipakka M, Poikonen K, Saksela K. SH3 domains with high affinity and engineered ligand specificities targeted to HIV-1 nef. J Mol Biol 1999;293:1097-106
9. Christ D, Winter G. Identification of protein domains by shotgun proteolysis. J Mol Biol 2006;358:364-71
10. Hwang WY, Foote J. Immunogenicity of engineered antibodies. Methods 2005;36:3-10
11. Leader B,Baca QJ,Golan DE, Protein therapeutics: a summary and pharmacological classification, Nat Rev Drug Discov, 2008, 7, 21-39.
12. Highsmith J. Biologic therapeutic drugs: technologies and global markets. 2013; BIO079B, BCC Research, Wellesley, MA 02481, USA
13. Bosklopper E. Antibody drugs: technologies and global markets. 2012; BIO016H, BCC Research, Wellesley, MA 02481, USA
14. Reichert JM. Marketed therapeutic antibodies compendium. MAbs 2012;4:413-15
15. Dall'Acqua WF, Cook KE, Damschroder MM, et al. Modulation of the effector functions of a human IgG1 through engineering of its hinge region. J Immunol 2006;177:1129-38
16. Dall'Acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal fc receptor (FcRn). J Biol Chem 2006;281:23514-24
17. Presta LG. Molecular engineering and design of therapeutic antibodies. Curr Opin Immunol 2008;20:460-70
18. Yeung YA, Leabman MK, Marvin JS, et al. Engineering human IgG1 affinity t o human neonatal fc receptor: impact of affinity improvement on pharmacokinetics in primates. J Immunol 2009;182:7663-71
19. Kubota T, Niwa R, Satoh M, et al. Engineered therapeutic antibodies with improved effector functions. Cancer Sci 2009;100:1566-72
20. Hinton PR, Xiong JM, Johlfs MG, et al. An engineered human IgG1 antibody with longer serum half-life. J Immunol 2006;176:346-56
21. Schreiber S, Khaliq-Kareemi M, Lawrance IC, PRECISE 2 Study Investigators. Maintenance therapy with certolizumab pegol for crohn's disease. N Engl J Med 2007;357:239-50
22. Winter TA, Sandborn WJ, de Villiers WJ, Schreiber S. Treatment of crohn's disease with certolizumab pegol. Expert Rev Clin Immunol 2007;3:683-94
23. Rutgeerts P, Schreiber S, Feagan B, et al. CDP870 Crohn's Disease Study Group. Certolizumab pegol, a monthly subcutaneously administered fc-free anti-TNFalpha, improves health-related quality of life in patients with moderate to severe crohn's disease. Int J C olorectal Dis 2008;23:289-96
24. Weinblatt ME, Fleischmann R, Huizinga TW, et al. Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results f rom the REALISTIC phase IIIb study. Rheumatology (Oxford) 2012;51:2204-14
25. Deeks ED. Certolizumab pegol: a review of its use in the management of rheumatoid arthritis. Drugs 2013;73:75-97
26. Qiu XQ, Wang H, Cai B, et al. Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting. Nat Biotechnol 2007;25:921-9
27. Chames P, Van Regenmortel M, Weiss E, Baty D. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 2009;157:220-33
28. Hansel TT, Kropsh ofer H, Singer T, et al. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 2010;9:325-38
29. Skerra A. Alternative non-antibody scaffolds for molecular recognition. Curr Opin Biotechnol 2007;18:295-304
30. Gebauer M, Skerra A. Engineered protein scaffolds as next-generation antibody therapeutics. Curr Opin Chem Biol 2009;13:245-55
31. Wesolowski J, Alzogaray V, Reyelt J, et al. Single domain antibodies: promising experimental and therapeutic tools in infection and immunity. Med Microbiol Immunol 2009;198:157-74
32. Lo fblom J, Frejd FY, Stahl S. Non-immunoglobulin based protein scaffolds. Curr Opin Biotechnol 2011;22:843-8
33. Wurch T,Pierre A,Depil S, Novel protein scaffolds as emerging therapeutic proteins: from discovery to clinical proof-of-concept, Trends Biotechnol, 2012, 30, 575-82.
34. Boersma YL, Pluckthun A. DARPins and other repeat protein scaffolds: advances in engineering and applications. Curr Opin Biotechnol 2011;22:849-57
35. Greenberg AS, Avila D, Hughes M, et al. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks . Nature 1995;374:168-73
36. Roux KH, Greenberg AS, Greene L, et al. Structural analysis of the nurse shark (new) antigen receptor (NAR): molecular convergence of NAR and unusual mammalian immuno globulins. Proc Natl Acad Sci USA 1998;95:11804-9
37. Streltsov VA, Varghese JN, Carmichael JA, et al. Structural evidence for evolution of shark ig new antigen receptor variable domain antibodie s from a cell-surface receptor. Proc Natl Acad Sci USA 2004;101:12444-9
38. Richards MH, Nelson JL. The evolution of vertebrate antigen receptors: a phylogenetic approach. Mol Biol Evol 2000;17:146-55
39. Dooley H, Flajnik MF. Shark immunity bites back: affinity maturation and memory response in the nurse shark, ginglymostoma cirratum. Eur J Immunol 2005;35:936-45
40. Dooley H, Flajnik MF. Antibody repertoire development in cartilaginous fish. Dev Comp Immunol 2006;30:43-56
41. Barelle C, Gill DS, Charlton K. Shark novel antigen receptors-the next generation of biologic therapeutics? Adv Exp Med Biol 2009;655:49-62
42. Stanfield RL, Dooley H, Flajnik MF, Wilson IA. Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Science 2004;305:1770-3
43. Stanfield RL, Dooley H, Verdino P, et al. Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding. J Mol Biol 2007;367:358-72
44. Diaz M, Stanfield RL, Greenberg AS, Flajnik MF. Structural analysis, selection, and ontogeny of the shark new antigen receptor (IgNAR): identification of a new locus preferentially expressed in early development. Immunogenetics 2002;54:501-12
45. Liu JL, Anderson GP, Delehanty JB, et al. Selection of cholera toxin specific IgNAR single-domain antibodies from a naive shark library. Mol Immunol 2007;44:1775-83
46. Nuttall SD, Krishnan UV, Doughty L, et al. A naturally occurring NAR variable domain binds the kgp protease from porphyromonas gingivalis. FEBS Lett 2002;516:80-6
47. Nuttall SD, Krishnan UV, Doughty L, et al. Isolation and characterization of an IgNAR variable domain specific for the human mitochondrial translocase receptor Tom70. Eur J Bioc hem 2003;270:3543-54
48. Nuttall SD, Humberstone KS, Krishnan UV, et al. Selection and affinity maturation of IgNAR variable domains targeting plasmodium falciparum AMA1. Proteins 2004;55:187-97
49. Dooley H, Flajnik MF, Porter AJ. Selection and characterization of naturally occurring single-domain (IgNAR) antibody fragments from immunized sharks by phage display. Mol Immunol 2003;40:25-33
50. Goodchild SA, Dooley H, Schoepp R J, et al. Isolation and characterisation of ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries. Mol Immunol 2011;48:2027-37
51. Mü ller MR, Saunders K, Grace C, et al. Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain. MAbs 2012;4:673
52. Bojalil R, Mata-Gonzalez MT, Sanchez-Munoz F, et al. Anti-tum or necrosis factor VNAR single domains reduce lethality and regulate underlying inflammatory response in a murine model of endotoxic shock. BMC Immunol 2013;14:17
53. Griffiths K, Dolezal O, Parisi K, et al. Shark variable new antigen receptor (VNAR) single domain antibody fragments: stability and diagnostic applications. Antibodies 2013;2:66-81
54. Liu JL,Zabetakis D,Brown JC,et al, Thermal stability and refolding capability of shark derived single domain antibodies, Mol Immunol, 2014, 59, 194-9.
55. Liu JL, Anderson GP, Goldman ER. Isolation of anti-toxin single domain antibodies from a semi-synthetic spiny dogfish shark display library. BMC Biotechnol 2007;7:78
56. Camacho-Villegas T, Mata-Gonzalez T, Pani agua-Solis J, et al. Human TNF cytokine neutralization with a vNAR from heterodontus francisci shark: a potential therapeutic use. MAbs 2013;5:80-5
57. Flajnik MF, Dooley H. The generation and selection of single-domain, v region libraries from nurse sharks. Methods Mol Biol 2009;562:71-82
58. Muller MR, O'Dwyer R, Kovaleva M, et al. Generation and isolation of targetspecific single-do main antibodies from shark immune repertoires. Methods Mol Biol 2012;907:177-94
59. Shao CY, Secombes CJ, Porter AJ. Rapid isolation of IgNAR variable singledomain antibody fragments from a shark synthetic library. Mol Immunol 2007;44:656-65
60. Simmons DP, Streltsov VA, Dolezal O, et al. Shark IgNAR antibody mimotopes target a murine immunoglobulin through extended CDR3 loop structures. Proteins 2008;71:119-30
61. Nuttall SD, Krishnan UV, Hattarki M, et al. Isolation of the new antigen receptor from wobbegong sharks, and use as a scaffold for the display of protein loop libraries. Mol Immunol 2001;38:313-26
62. Walsh R, Nuttall S, Revill P, et al. Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody. Virology 2011;411:132-41
63. Ohtani M, Hikima J, Jung TS, et al. Variable domain antibodies specific for viral hemorrhagic septicemia virus (VHSV) selected from a randomized IgNAR phage display library. Fish Shellf ish Immunol 2013;34:724-8
64. Ohtani M, Hikima J, Jung TS, et al. Construction of an artificially randomized IgNAR phage display library: screening of variable regions that bind to hen egg white lyso zyme. Mar Biotechnol (NY) 2013;15:56-62
65. Fennell BJ, Darmanin-Sheehan A, Hufton SE, et al. Dissection of the IgNAR V domain: molecular scanning and orthologue database mining define novel IgN AR hallmarks and affinity maturation mechanisms. J Mol Biol 2010;400:155-70
66. Kovalenko OV, Olland A, Piche-Nicholas N, et al. Atypical antigen recognition mode of a shark IgNAR variable domai n characterized by humanization and structural analysis. J Biol Chem 2013;288(24):17408-19
67. Schmidt MM, Wittrup KD. A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol Cancer Ther 2009;8:2861-71
68. Obeidat M, Obeidat M, Ballermann BJ. Glomerular endothelium: a porous sieve and formidable barrier. Exp Cell Res 2012;318:964-72
69. Kitamura K, Takahashi T, Yamaguchi T, et al. Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy. Cancer Res 1991;51:4310-15
70. Chapman AP, Antoniw P, Spitali M, et al. Therapeutic antibody fragments with prolonged in vivo half-lives. Nat Biotechnol 1999;17:780-3
71. Jevsevar S, Kunstelj M, Porekar VG. PEGylation of therapeutic proteins. Biotechnol J 2010;5:113-28
72. Stork R, Zettlitz KA, Muller D, et al. N-glycosylation as novel strategy to improve pharmacokinetic properties of bispecific single-chain diabodies. J Biol Chem 2008;283:7804-12
73. Smith BJ, Popplewell A, Athwal D, et al. Prolonged in vivo residence times of antibody fragments associated with albumin. Bioconjug Chem 2001;12:750-6
74. Ku rtzhals P, Havelund S, Jonassen I, et al. Albumin binding of insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo. Bi ochem J 1995;312(Pt 3):725-31
75. Makrides SC,Nygren PA,Andrews B,et al, Extended in vivo half-life of human soluble complement receptor type 1 fused to a serum albumin-binding receptor, J Phar macol Exp Ther, 1996, 277, 534-42.
76. Muller D, Karle A, Meissburger B, et al. Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J Biol Chem 2007;282:12650-60
77. Markussen J, Havelund S, Kurtzhals P, et al. Soluble, fatty acid acylated insulins bind to albumin and show protracted action in pigs. Diabetologia 1996;39:281-8
78. Stork R, Muller D, Kontermann RE. A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecific single-chain diabody with an albuminbinding domain from st reptococcal protein G. Protein Eng Des Sel 2007;20:569-76
79. Dennis MS, Zhang M, Meng YG, et al. Albumin binding as a general strategy for improving the pharmacokinetics of proteins. J Biol Chem 2002;277:35035-43
80. Nguyen A, Reyes AE II, Zhang M, et al. The pharmacokinetics of an albuminbinding fab (AB.fab) can be modulated as a function of affinity for albumin. Protein Eng Des S el 2006;19:291-7
81. Alt M, Muller R, Kontermann RE. Novel tetravalent and bispecific IgG-like antibody molecules combining singlechain diabodies with the immunoglobulin gamma1 fc or CH3 region. FEBS Lett 1999;454:90-4
82. Strohl W, Strohl L. Therapeutic antibody engineering: current and future advances driving the strongest growth area in the pharmaceutical industry. Woodhead Publishing, Cambridge, UK; 2012
83. Teillaud JL. From whole monoclonal antibodies to single domain antibodies: think small. Methods Mol Biol 2012;911:3-13
84. Buss NA, H enderson SJ, McFarlane M, et al. Monoclonal antibody therapeutics: history and future. Curr Opin Pharmacol 2012;12:615-22
85. Ahmad ZA, Yeap SK, Ali AM, et al. scFv antibody: principles and clinical application. Clin Dev Immunol 2012;2012:980250
86. McAleese F, Eser M. RECRUITTandAbs: harnessing the immune system to kill cancer cells. Future Oncol 2012;8:687-95
87. Hamers-Casterman C, Atarhouch T, Muyldermans S, et al. Naturally occurring antibodies devoid of light chains. Nature 1993;363:446-8
88. Ignatovich O, Jespers L, Tomlinson IM, de Wildt RM. Creation of the large and highly functional synthetic repertoire of human VH and vkappa domain antibodies. Methods Mol Biol 2012;911:39-63
89. Holt LJ, Basran A, J ones K, et al. Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs. Protein Eng Des Sel 2008;21:283-8
90. Walker A, Dunlevy G, Rycroft D, et al. Anti-s erum albumin domain antibodies in the development of highly potent, efficacious and long-acting interferon. Protein Eng Des Sel 2010;23:271-8
91. Skerra A. Engineered protein scaffolds for molecular recognition. J Mol Recognit 2000;13:167-87
92. Binz HK, Amstutz P, Pluckthun A. Engineering novel binding proteins from nonimmunoglobulin domains. Nat Biotechnol 2005;23:1257-68
93. Nuttall SD, Walsh RB. Display scaffolds: protein engineering for novel therapeutics. Curr Opin Pharmacol 2008;8:609-15
94. Lehmann A. Ecallantide (DX-88), a plasma kallikrein inh ibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery. Expert Opin Biol Ther 2008;8:1187-99
95. Delacourt C, Herigault S, Delclaux C, et al. Protection against acute lung injury by intravenous or intratracheal pretreatment with EPI-HNE-4, a new potent neutrophil elastase inhibitor. Am J Respir Cell Mol Biol 2002;26:290-7
96. Honore S, Attalah HL, Azoulay E, et al. Beneficial effect of an inhibitor of leukocyte elastase (EPI-hNE-4) in presence of repeated lung injuries. Shock 2004;22:131-6
97. Attucci S,Gauthier A,Korkmaz B,et al., EPI-hNE4, a proteolysis-resistant inhibitor of human neutrophil elastase and potential anti-inflammatory drug for treating cystic fibrosis, J Pharmacol Exp Ther, 2006, 318, 803-9.
98. Feldwisch J, Tolmachev V. Engineering of affibody molecules for therapy and diagnostics. Methods Mol Biol 2012;899:103-26
99. Bloom L, Calabro V. FN3: a new protein scaffold reaches the clinic. Drug Discov Today 2009;14:949-55
100. Lipovsek D. Adnectins: engineered target-binding protein therapeutics. Protein Eng Des Sel 2011;24:3-9
101. Tolcher AW, Sweeney CJ, Papadopoulos K, et al. Phase I and pharmacokinetic study of CT-322 (BMS-844203), a targeted adnectin inhibitor of VEGFR-2 based on a domain of human fibronectin. Clin Cancer Res 2011;17:363 -71
102. Richter A, Eggenstein E, Skerra A. Anticalins: exploiting a non-ig scaffold with hypervariable loops for the engineering of binding proteins. FEBS Lett 2014;588:213-18
103. . De Meyer T, Muyldermans S, Depicker A. Nanobody-based products as research and diagnostic tools. Trends Biotechnol 2014;32:263-70
104. De Vos J, Devoogdt N, Lahoutte T, Muyldermans S. Camelid single-domain antibody-fragment engineering for (pre) clinical in vivo molecular imaging applications: adjusting the bullet to its target. Expert Opin Biol Ther 2013;13:1149-60
105. Clinical Tr ials.gov. 2014. Available from: http://www.clinicaltrials.gov/[Last accessed 2 May 2014]
106. Molecular Partners. 2014. Available from: http://www. molecularpartners.com/public/index.php? id=23&lang=en [Last accessed 2 May 2014]
107. Ablynx. 2014. Available from: http://www.ablynx.com/en/researchdevelopment/pipeline/[Last accessed 2 May 2014]