ФАГОВЫЙ ДИСПЛЕЙ В КОНСТРУИРОВАНИИ АНТИТЕЛ С ЗАДАННЫМИ СВОЙСТВАМИ
Уникальная особенность моноклональных антител высокоспецифично взаимодействовать с молекулярными мишенями позволила им занять ведущее положение в терапии онкологических и аутоиммунных заболеваний, стать незаменимым инструментом протеомных исследований и компонентом диагностических систем. Представлен обзор новейших литературных данных по использованию метода фагового дисплея для получения рекомбинантных антител, которые другими методами получить невозможно, а также собственные оригинальные результаты в этой области. На основании бионформационного анализа структур депонированных комплексов антител с антигенами нами создана комбинаторная библиотеки Fab фрагментов антител человека, обладающая разнообразием более 1010 независимых клонов и способная служить источником рекомбинантных антител. С использованием негативной селекции нами получены и характеризованы высокоспецифичные однодоменные антитела к альдостерон-синтазе (цитохром Р45011В2, CYP11B2), не обладающие в ИФА кросс-реактивностью с ее гомологом CYP11B1 (93% идентичности последовательностей), а также антитела к таким высокомолекулярным мишеням, как эритропоэтин, соматотропный гормон и тиреопероксидаза человека.
1. Recent advances in the application of antibodies as therapeutics / R. E. Burden [et al.] // Future Med. Chem. – 2012. – Vol. 4, № 1. – P. 73–86.
2. Antibodies in diagnostics – from immunoassays to protein chips / C. A. Borrebaeck // Immunol. Today. – 2000. – Vol. 21, № 8. – P. 379–382.
3. Rodgers, K. R. Therapeutic monoclonal antibodies and derivatives: Historical perspectives and future directions / K. R. Rodgers, R. C. Chou // Biotechnol. Adv. – 2016. – Vol. 34, № 6. – P. 1149–1158.
4. Ecker, D. M. The therapeutic monoclonal antibody market / D. M. Ecker, S. D. Jones, H. L. Levine // MAbs. – 2015. – Vol. 7, № 1. – P. 9–14.
5. Antibodies for profiling the human proteome-The Human Protein Atlas as a resource for cancer research / A. Asplund [et al.] // Proteomics. – 2012. – Vol. 12, № 13. – P. 2067–2077.
6. Towards a knowledge-based Human Protein Atlas / M. Uhlen [et al.] // Nat. Biotechnol. – 2010. – Vol. 28, № 12. – P. 1248–1250.
7. Buchner, J. Renaturation, purification and characterization of recombinant Fab-fragments produced in Escherichia coli / J. Buchner, R. Rudolph // Biotechnology (N Y). – 1991. – Vol. 9, № 2. – P. 157–162.
8. Rousseaux, J. Optimal conditions for the preparation of Fab and F(ab’)2 fragments from monoclonal IgG of different rat IgG subclasses / J. Rousseaux, R. Rousseaux-Prevost, H. Bazin // J. Immunol. Methods. – 1983. – Vol. 64, № 1–2. – P. 141–146.
9. Gaudreault, J. Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration / J. Gaudreault [et al.] // Invest. Ophthalmol. Vis. Sci. – 2005. – Vol. 46, № 2. – P. 726–733.
10. Single-chain antigen-binding proteins / R. E. Bird [et al.] // Science. – 1988. – Vol. 242, № 4877. – P. 423–426.
11. Recombinant Immunotoxin 4D5scFv-PE40 for Targeted Therapy of HER2-Positive Tumors / E. A. Sokolova [et al.] // Acta Naturae. – 2015. – Vol. 7, № 4. – P. 93–96.
12. Phase IB trial of chimeric antidisialoganglioside antibody plus interleukin 2 for melanoma patients / M. R. Albertini [et al.] // Clin. Cancer Res. – 1997. – Vol. 3, № 8. – P. 1277–1288.
13. Vial, T. Immune-mediated side-effects of cytokines in humans / T. Vial, J. Descotes // Toxicology. – 1995. – Vol. 105, № 1. – P. 31–57.
14. An anti-MUC1-antibody-interleukin-2 fusion protein that activates resting NK cells to lysis of MUC1-positive tumour cells / C. Heuser [et al.] // Br. J. Cancer. – 2003. – Vol. 89, № 6. – P. 1130–1139.
15. Penichet, M. L. An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity / M. L. Penichet, E. T. Harvill, S. L. Morrison // J. Interferon Cytokine Res. – 1998. – Vol. 18, № 8. – P. 597–607.
16. Clementschitsch, F. Improvement of bioprocess monitoring: development of novel concepts / F. Clementschitsch, K. Bayer // Microb. Cell Fact. – 2006. – Vol. 5. P. 19.
17. Development of CYB5-fusion monitoring system for efficient periplasmic expression of multimeric proteins in Escherichia coli / D. Dormeshkin [et al.] // Protein Expr. Purif. – 2016. – Vol. 128. – P. 60–66.
18. The crystal structure of a llama heavy chain variable domain / S. Spinelli [et al.] // Nat. Struct. Biol. – 1996. – Vol. 3, № 9. – P. 752–757.
19. Structural insights and biomedical potential of IgNAR scaffolds from sharks / S. Zielonka [et al.] // MAbs. – 2015. – Vol. 7, № 1. – P. 15–25.
20. Rouet, R. Generation of human single domain antibody repertoires by Kunkel mutagenesis / R. Rouet, K. Dudgeon, D. Christ // Methods Mol. Biol. – 2012. – Vol. 907. – P. 195–209.
21. Camelid single-domain antibody-fragment engineering for (pre)clinical in vivo molecular imaging applications: adjusting the bullet to its target / J. De Vos [et al.] // Expert Opin. Biol. Ther. – 2013. – Vol. 13, № 8. – P. 1149–1160.
22. The preclinical pharmacology of the high affinity anti-IL-6R Nanobody(R) ALX-0061 supports its clinical development in rheumatoid arthritis / M. Van Roy [et al.] // Arthritis Res. Ther. – 2015. – Vol. 17. – P. 135.
23. Holz, J. B. The TITAN trial--assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura / J. B. Holz // Transfus. Apher. Sci. – 2012. – Vol. 46, № 3. – P. 343–346.
24. Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection / L. Detalle [et al.] // Antimicrob. Agents Chemother. – 2015. – Vol. 60, № 1. – P. 6–13.
25. Detection of carcinoembryonic antigen using single-domain or full-size antibodies stained with quantum dot conjugates / G. Rousserie [et al.] // Anal. Biochem. – 2015. – Vol. 478. – P. 26–32.
26. Schroeder, K. L. Graphene Quantum Dots for Theranostics and Bioimaging / K. L. Schroeder, R. V. Goreham, T. Nann // Pharm. Res. – 2016. – Vol. 33, № 10. – P. 2337–2357.
27. Directed evolution of PDZ variants to generate high-affinity detection reagents / M. Ferrer [et al.] // Protein Eng. Des. Sel. – 2005. – Vol. 18, № 4. – P. 165–173.
28. Hosse, R. J. A new generation of protein display scaffolds for molecular recognition / R. J. Hosse, A. Rothe, B. E. Power // Protein Sci. – 2006. – Vol. 15, № 1. – P. 14–27.
29. Sedgwick, S. G. The ankyrin repeat: a diversity of interactions on a common structural framework / S. G. Sedgwick, S. J. Smerdon // Trends Biochem. Sci. – 1999. – Vol. 24, № 8. – P. 311–316.
30. Directed evolution to low nanomolar affinity of a tumor-targeting epidermal growth factor receptor-binding affibody molecule / M. Friedman [et al.] // J. Mol. Biol. – 2008. – Vol. 376, № 5. – P. 1388–1402.
31. Kohler, G. Continuous cultures of fused cells secreting antibody of predefined specificity / G. Kohler, C. Milstein // Nature. – 1975. – Vol. 256, № 5517. – P. 495–497.
32. Ruberti, F. Cloning and expression of an anti-nerve growth factor (NGF) antibody for studies using the neuroantibody approach / F. Ruberti, A. Bradbury, A. Cattaneo // Cell. Mol. Neurobiol. – 1993. – Vol. 13, № 5. – P. 559–568.
33. An improved method for generating single-chain antibodies from hybridomas / P. J. Nicholls [et al.] // J. Immunol. Methods. – 1993. – Vol. 165, № 1. – P. 81–91.
34. Structure-based affinity maturation of a chimeric anti-ricin antibody C4C13 / L. Luo [et al.] // J. Biomol. Struct. Dyn. – 2014. – Vol. 32, № 3. – P. 416–423.
35. Ikonomova, S. P. A simple and robust approach to immobilization of antibody fragments / S. P. Ikonomova, Z. He, A. J. Karlsson // J. Immunol. Methods. – 2016. – Vol. 435. – P. 7–16.
36. Toleikis, L. Cloning single-chain antibody fragments (ScFv) from hyrbidoma cells / L. Toleikis, A. Frenzel // Methods Mol. Biol. – 2012. – Vol. 907. № – P. 59–71.
37. Generation and characterization of biotinylated recombinant Fab antibody fragment against cortisol / D. O. Dor- meshkin [et al.] // Russian Journal of Bioorganic Chemistry. – 2016. – Vol. 42, № 1. – P. 7.
38. Tomita, M. Hybridoma technologies for antibody production / M. Tomita, K. Tsumoto // Immunotherapy. – 2011. – Vol. 3, № 3. – P. 371–380.
39. Smith, G. P. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface / G. P. Smith // Science. – 1985. – Vol. 228, № 4705. – P. 1315–1317.
40. Beyond natural antibodies: the power of in vitro display technologies / A. R. Bradbury [et al.] // Nat. Biotechnol. – 2011. – Vol. 29, № 3. – P. 245–254.
41. Application of phage display to high throughput antibody generation and characterization / D. J. Schofield [et al.] // Genome Biol. – 2007. – Vol. 8, № 11. – P. R254.
42. Carmen, S. Concepts in antibody phage display / S. Carmen, L. Jermutus // Brief. Funct. Genomic Proteomic. – 2002. – Vol. 1, № 2. – P. 189–203.
43. Significant impact of single N-glycan residues on the biological activity of Fc-based antibody-like fragments / J. Jez [et al.] // J. Biol. Chem. – 2012. – Vol. 287, № 29. – P. 24313–24319.
44. Watkins, N. A. Introduction to antibody engineering and phage display / N. A. Watkins, W. H. Ouwehand // Vox Sang. – 2000. – Vol. 78, № 2. – P. 72–79.
45. Griffiths, A. D. Strategies for selection of antibodies by phage display / A. D. Griffiths, A. R. Duncan // Curr. Opin. Biotechnol. – 1998. – Vol. 9, № 1. – P. 102–108.
46. Making antibody fragments using phage display libraries / T. Clackson [et al.] // Nature. – 1991. – Vol. 352, № 6336. – P. 624–628.
47. Sok, D. HIV Broadly Neutralizing Antibodies: Taking Good Care Of The 98 / D. Sok, D. R. Burton // Immunity. – 2016. – Vol. 45, № 5. – P. 958–960.
48. Recombinant anti-P protein autoantibodies isolated from a human autoimmune library: reactivity, specificity and epitope recognition / S. Zampieri [et al.] // Cell. Mol. Life Sci. – 2003. – Vol. 60, № 3. – P. 588–598.
49. Hoogenboom, H. R. By-passing immunisation. Human antibodies from synthetic repertoires of germline VH gene segments rearranged in vitro / H. R. Hoogenboom, G. Winter // J. Mol. Biol. – 1992. – Vol. 227, № 2. – P. 381–388.
50. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides / A. Knappik [et al.] // J. Mol. Biol. – 2000. – Vol. 296, № 1. – P. 57–86.
51. A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties / T. Tiller [et al.] // MAbs. – 2013. – Vol. 5, № 3. – P. 445–470.
52. The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies / C. Rothe [et al.] // J. Mol. Biol. – 2008. – Vol. 376, № 4. – P. 1182–1200.
53. Construction of a Semisynthetic Human VH Single-Domain Antibody Library and Selection of Domain Antibodies against alpha-Crystalline of Mycobacterium tuberculosis / N. H. Hairul Bahara [et al.] // J Biomol Screen. – 2016. – Vol. 21, № 1. – P. 35–43.
54. Eteshola, E. Isolation of scFv fragments specific for monokine induced by interferon-gamma (MIG) using phage display / E. Eteshola // J. Immunol. Methods. – 2010. – Vol. 358, № 1–2. – P. 104–10.
55. Development of a novel human scFv against EGFR L2 domain by phage display technology / L. Rahbarnia [et al.] // Curr. Pharm. Des. – 2016. – Vol. № – P.
56. Human combinatorial Fab library yielding specific and functional antibodies against the human fibroblast growth factor receptor 3 / R. Rauchenberger [et al.] // J. Biol. Chem. – 2003. – Vol. 278, № 40. – P. 38194–38205.
57. Padlan, E. A. Anatomy of the antibody molecule / E. A. Padlan // Mol Immunol. – 1994. – Vol. 31, № 3. – P. 169–217.
58. Padlan, E. A. Does base composition help predispose the complementarity-determining regions of antibodies to hy-permutation? / E. A. Padlan // Mol. Immunol. – 1997. – Vol. 34, № 11. – P. 765–770.
59. Tyrosine plays a dominant functional role in the paratope of a synthetic antibody derived from a four amino acid code / F. A. Fellouse [et al.] // J. Mol. Biol. – 2006. – Vol. 357, № 1. – P. 100–114.
60. Ho, S. Y. Electroporation of cell membranes: a review / S. Y. Ho, G. S. Mittal // Crit. Rev. Biotechnol. – 1996. – Vol. 16, № 4. – P. 349–362.
61. Phage display antibodies for diagnostic applications / N. H. Hairul Bahara [et al.] // Biologicals. – 2013. – Vol. 41, № 4. – P. 209–216.
62. Igawa, T. pH-dependent antigen-binding antibodies as a novel therapeutic modality / T. Igawa, F. Mimoto, K. Hattori // Biochim. Biophys. Acta. – 2014. – Vol. 1844, № 11. – P. 1943–1950.
63. De novo isolation of antibodies with pH-dependent binding properties / P. Bonvin [et al.] // MAbs. – 2015. – Vol. 7, № 2. – P. 294–302.
64. The multiple roles of histidine in protein interactions / S. M. Liao [et al.] // Chem Cent J. – 2013. – Vol. 7, № 1. – P. 44.
65. Allosteric control of ligand-binding affinity using engineered conformation-specific effector proteins / S. S. Rizk [et al.] // Nat. Struct. Mol. Biol. – 2011. – Vol. 18, № 4. – P. 437–442.
66. Crystal structure of full-length KcsA in its closed conformation / S. Uysal [et al.] // Proc. Nat. Acad. Sci. U S A. – 2009. – Vol. 106, № 16. – P. 6644–6649.
67. Rainey, W. E. Adrenal zonation: clues from 11beta-hydroxylase and aldosterone synthase / W. E. Rainey // Mol. Cell. Endocrinol. – 1999. – Vol. 151, № 1–2. – P. 151–60.
68. Structural insights into aldosterone synthase substrate specificity and targeted inhibition / N. Strushkevich [et al.] // Mol. Endocrinol. – 2013. – Vol. 27, № 2. – P. 315–324.
69. Development of monoclonal antibodies against human CYP11B1 and CYP11B2 / C. E. Gomez-Sanchez [et al.] // Mol. Cell. Endocrinol. – 2014. – Vol. 383, № 1–2. – P. 111–117.
70. Application of Bio-Layer Interferometry for the analysis of protein/liposome interactions / Wallner, J. [et al.] // J. Pharm. Biomed. Anal. – 2013. – Vol. 72, № – P. 150–154.
71. HuCAL PLATINUM, a synthetic Fab library optimized for sequence diversity and superior performance in mammalian expression systems / J. Prassler [et al.] // J. Mol. Biol. – 2011. – Vol. 413, № 1. – P. 261–278.
72. Frenzel, A. Phage display-derived human antibodies in clinical development and therapy / A. Frenzel, T. Schirrmann, M. Hust // MAbs. – 2016. – Vol. 8, № 7. – P. 1177–1194.