Preview

Медицинская иммунология

Расширенный поиск

ОДНОДОМЕННЫЕ АНТИТЕЛА И БИОИНЖЕНЕРНЫЕ ПРЕПАРАТЫ НА ИХ ОСНОВЕ: НОВЫЕ ВОЗМОЖНОСТИ ДЛЯ ДИАГНОСТИКИ И ТЕРАПИИ

https://doi.org/10.15789/1563-0625-2016-6-505-520

Полный текст:

Аннотация

Около 20 лет назад у представителей семейства Camelidae в сыворотке крови были обнаружены особые неканонические антитела, состоящие только из укороченных тяжелых цепей при полном отсутствии легких. За узнавание антигена у этих необычных антител отвечает только один вариабельный домен. Рекомбинантный белок, являющийся аналогом или производным такого анти-ген-узнающего вариабельного домена, получил название «однодоменное антитело» (sdAb), или «нанотело» (nanobody), иногда также его называют «наноантитело». C тех пор однодоменные антитела (наноантитела) и их производные нашли широкое применение во многих областях биологии и медицины, открыли новые перспективы для решения таких значимых проблем, как диагностика и терапия рака, инфекционных и аутоиммунных заболеваний, а также нейтрализация ядов и токсинов. Этот обзор посвящен современным исследованиям с применением наноантител, а также освещает перспективы их использования для создания новых диагностических и терапевтических препаратов.

Об авторах

Е. Н. Горшкова
Центр молекулярной биологии и биомедицины института биологии и биомедициныФГАОУ ВО «Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского», г. Нижний Новгород, Россия
Россия
к.б.н., научный сотрудник лаборатории экспериментальной иммунологии


В. А. Василенко
Институт биологии и биомедицины ФГАОУ ВО «Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского», г. Нижний Новгород, Россия
Россия

аспирант, младший научный сотрудник лаборатории экспериментальной иммунологии центра молекулярной биологии и биомедицины 



С. В. Тиллиб
ФГБУН «Институт биологии гена» РАН, Москва, Россия
Россия

д.б.н., руководитель лаборатории молекулярных биотехнологий 



И. В. Астраханцева
Институт биологии и биомедицины ФГАОУ ВО «Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского», г. Нижний Новгород, Россия
Россия

к.б.н., научный сотрудник лаборатории экспериментальной иммунологии центра молекулярной биологии и биомедицины 



Список литературы

1. Астраханцева И.В., Ефимов Г.А., Друцкая М.С., Круглов А.А., Недоспасов С.А. Современная антицитокиновая терапия аутоиммунных заболеваний // Биохимия, 2014. Т. 79, № 12. С. 1607-1618. [Astrakhantseva I.V., Efimov G.A., Drutskaya M.S., Kruglov A.A., Nedospasov S.A. Modern anti-cytokine therapy of autoimmune diseases. Biokhimiya = Biochemistry, 2014, Vol. 79, no. 12, pp. 1308-1321. (In Russ.)]

2. Гарас М.Н., Тиллиб С.В., Зубкова О.В., Рогожин В.Н., Иванова Т.И., Васильев Л.А. Мишень-специфичная доставка генов с помощью рекомбинантных псевдоаденовирусных частиц, способных эффективно связываться с наноантителами // Acta Naturae (русскоязычная версия), 2014. Т. 2, № 6. С. 102-113. [Garas M.N., Tillib S.V., Zubkova O.V., Rogozhin V.N., Ivanova T.I., Vasilev I.A., Logunov D.Yu., Shmarov M.M., Tutykhina I.L., Esmagambetov I.B., Gribova I.Yu., Bandelyuk A.S., Naroditsky B.S., Gintsburg A.L. Construction of a pix-modified adenovirus vector able to effectively bind to nanoantibodies for targeting. Acta Naturae (russkoyazychnaya versiya) = Acta Naturae, 2014, Vol. 6, no. 2, pp. 95-105. (In Russ.)]

3. Ефимов Г.А., Хлопчатникова З.В., Сазыкин А.Ю., Друцкая М.С., Круглов А.А., Шилов Е.С., Кучмий А.А., Недоспасов С.А., Тиллиб. С. В. Получение и характеристика нового рекомбинантного однодоменного анти-тела, специфически связывающегося с TNF человека // Российский иммунологический журнал, 2012. Т. 6, № 4. С. 337-345. [Efimov G.A., Khlopchatnikova Z.V., Sazikin A.Yu., Drutskaya M.S., Kruglov A.A., Shilov E.S., Kuchmiy A.A., Nedospasov S.A., Tillib S.B. Isolation and characteristics of a new recombinant single domain antibody that specifically binds to human TNF. Rossiyskiy immunologicheskiy zhurnal = Russian Immunology Journal, Vol. 6, no. 4, pp. 337-345. (In Russ.)]

4. Тиллиб С.В. «Верблюжьи наноантитела» – эффективный инструмент для исследований, диагностики и терапии // Молекулярная биология, 2011. Т. 45, № 1. С. 77-85. [Tillib S.V. «Camel nanoantibody» is an efficient tool for research, diagnostics and therapy. Molekulyarnaya biologiya = Molecular Biology, 2011, Vol. 45, no. 1, pp. 66-73. (In Russ.)]

5. Тиллиб С.В., Вятчанин А.С., Муилдерманс С. Молекулярный анализ структуры особых антител Camelus bactrianus, состоящих только из тяжелых цепей // Биохимия, 2014. Т. 79, № 12. С. 1382-1390. Tillib S.V., Vyatchanin A.S., Muyldermans S. Molecular analysis of heavy chain-only antibodies of Camelus bactrianus. Biokhimiya = Biochemistry, 2014, Vol. 79, no. 12. pp. 1382-1390. (In Russ.)]

6. Тиллиб С.В., Иванова Т.И., Лысюк Е.Ю., Ларин С.С., Кибардин А.В., Коробко Е.В., Вихрева П.Н., Гнучев Н.В., Георгиев Г.П., Коробко И.В. Наноантитела для детекции и блокирования биологической активности фактора роста эндотелия сосудов A165 человека // Биохимия, 2012. Т. 77, № 6. С. 659-665. [Tillib S.V., Ivanova T.I., Lyssuk E.Yu., Larin S.S., Kibardin A.V., Korobko E.V., Vikhreva P.N., Gnuchev N.V., Georgiev G.P., Korobko I.V. Nanoantibodies for detection and blocking of bioactivity of human vascular endothelial growth factor A165. Biokhimiya = Biochemistry, 2012, Vol. 7, no. 6, pp. 659-665. (In Russ.)]

7. Abulrob A., Sprong H., van Bergen En Henegouwen P., Stanimirovic D. The blood-brain barrier transmigrating single domain antibody: Mechanisms of transport and antigenic epitopes in human brain endothelial cells. J. Neurochem., 2005, Vol. 95, pp. 1201-1214.

8. Abu-Yousif A.O., Moor A.C.E., Zheng X., Savellano M.D., Yu W., Selbo P.K., Hasan T. Epidermal growth factor receptor-targeted photosensitizer selectively inhibits EGFR signaling and induces targeted phototoxicity in ovarian cancer cells. Cancer Lett., 2012, Vol. 321, pp. 120-127.

9. Arbabi-Ghahroudi M., Tanha J., MacKenzie R. Prokaryotic expression of antibodies. Cancer Metastasis Rev., 2005, Vol. 24, pp. 501-519.

10. Ardekani L.S., Gargari S.L.M., Rasooli I., Bazl M.R., Mohammadi M., Ebrahimizadeh W., Bakherad H., Zare H. A novel nanobody against urease activity of Helicobacter pylori. Int. J. Infect. Dis., 2013, Vol. 17, pp. e723-e728.

11. Barrera D.J., Rosenberg J.N., Chiu J.G., Chang Y.-N., Debatis M., Ngoi S.-M., Chang J.T., Shoemaker C.B., Oyler G.A., Mayfield S.P. Algal chloroplast produced camelid VHH antitoxins are capable of neutralizing botulinum neurotoxin. Plant Biotechnol. J., 2015, Vol. 73, pp. 389-400.

12. Beekwilder J., van Houwelingen A., van Beckhoven J., Speksnijder A. Stable recombinant alpaca antibodies for detection of Tulip virus X. Eur. J. Plant Pathol., 2008, Vol. 121, pp. 477-485.

13. Behdani M., Zeinali S., Khanahmad H., Karimipour M., Asadzadeh N., Azadmanesh K., Khabiri A., Schoonooghe S., Habibi Anbouhi M., Hassanzadeh-Ghassabeh G., Muyldermans S. Generation and characterization of a functional Nanobody against the vascular endothelial growth factor receptor-2; angiogenesis cell receptor. Mol. Immunol. Elsevier Ltd, 2012, Vol. 50, pp. 35-41.

14. Bond C.J., Marsters J.C., Sidhu S.S. Contributions of CDR3 to VHH domain stability and the design of monobody scaffolds for naive antibody libraries. J. Mol. Biol., 2003, Vol. 332, pp. 643-655.

15. Bruce V.J., Lopez-Islas M., McNaughton B.R. Resurfaced cell-penetrating nanobodies: A potentially general scaffold for intracellularly targeted protein discovery. Protein Sci., 2016, Vol. 25, no. 6, pp. 1129-1137.

16. Buchfellner A., Yurlova L., Nüske S., Scholz A.M., Bogner J., Ruf B., Zolghadr K., Drexler S.E., Drexler G.A., Girst S., Greubel, Reindl C., Siebenwirth J., Romer C., Friedl T., Friedl A.A., Rothbauer U. A new nanobody-based biosensor to study endogenous PARP1 In vitro and in live human cells. PLoS One, 2016, Vol. 11, p. e0151041.

17. Burgess A., Lorca T., Castro A. Quantitative live imaging of endogenous DNA replication in mammalian cells. PLoS One, 2012, Vol. 7, pp. e45726.

18. Burmistrova D.A., Tillib S.V., Shcheblyakov D., Dolzhikova I.V., Shcherbinin D.N., Zubkova O.V., Ivanova T.I., Tukhvatulin A.I., Shmarov M.M., Logunov D.Y., Naroditsky B.S., Gintsburg A.L. Genetic passive immunization with adenoviral vector expressing chimeric nanobody-Fc molecules as therapy for genital infection caused by Mycoplasma hominis. PLoS One, 2016, Vol. 11, pp. e0150958.

19. Calpe S., Wagner K., El Khattabi M., Rutten L., Zimberlin C., Dolk E., Verrips C.T., Medema J.P., Spits H., Krishnadath K.K. Effective inhibition of bone morphogenetic protein function by highly specific llama-derived antibodies. Mol. Cancer Ther., 2015, Vol. 14, pp. 2527-2540.

20. Chen J., Davé S.K., Simmons A. Prevention of genital herpes in a guinea pig model using a glycoprotein D-specific single chain antibody as a microbicide. Virol. J., 2004, Vol. 1. p. 11.

21. Conrad U., Plagmann I., Malchow S., Sack M., Floss D.M., Kruglov A.A., Nedospasov S.A., Rose-John S., Scheller J. ELPylated anti-human TNF therapeutic single-domain antibodies for prevention of lethal septic shock. Plant Biotechnol. J., 2011, Vol. 9, no. 1, pp. 22-31.

22. Conrath K.E., Lauwereys M., Galleni M., Matagne A., Frère J.M., Kinne J., Wyns L., Muyldermans S. β-Lactamase inhibitors derived from single-domain antibody fragments elicited in the Camelidae. Antimicrobial Agents and Chemotherapy, 2001, Vol. 45, no. 10, pp. 2807-2812.

23. Conrath K.E., Wernery U., Muyldermans S., Nguyen V.K. Emergence and evolution of functional heavy-chain antibodies in Camelidae. Dev. Comp. Immunol., 2003, Vol. 27, no. 2, pp. 87-103.

24. Coppieters K., Dreier T., Silence K., de Haard H., Lauwereys M., Casteels P., Beirnaert E., Jonckheere H., van de Wiele C., Staelens L., Hostens J., Revets H., Remaut E., Elewaut D., Rottiers P. Formatted anti-tumor necrosis factor α VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen-induced arthritis. Arthritis Rheum., 2006, Vol. 54, no. 6, pp. 1856-1866.

25. Cortez-Retamozo V., Backmann N., Senter P., Wernery U., de Baetselier P. Efficient cancer therapy with a nanobody-based conjugate. Cancer Res., 2004, Vol. 64, pp. 2853-2857.

26. Cortez-Retamozo V., Lauwereys M., Hassanzadeh Gh.G., Gobert M., Conrath K., Muyldermans S., De Baetselier P., Revets H. Efficient tumor targeting by single-domain antibody fragments of camels. Int. J. Cancer, 2002, Vol. 98, no. 3, pp. 456-462.

27. D’Huyvetter M., Xavier C., Caveliers V., Lahoutte T., Muyldermans S., Devoogdt N. Radiolabeled nanobodies as theranostic tools in targeted radionuclide therapy of cancer. Expert Opin. Drug Deliv., 2014, Vol. 11, no. 12, pp. 1939-1954.

28. Darvish M., Behdani M., Shokrgozar M.A., Pooshang-Bagheri K., Shahbazzadeh D. Development of protective agent against Hottentotta saulcyi venom using camelid single-domain antibody. Mol. Immunol. Elsevier Ltd, 2015, Vol. 68, no. 2, pp. 412-420.

29. de Buck S., Nolf J., de Meyer T., Virdi V., de Wilde K., van Lerberge E., van Droogenbroeck B., Depicker A. Fusion of an Fc chain to a VHH boosts the accumulation levels in arabidopsis seeds. Plant Biotechnol. J., 2013, Vol. 11, no. 8, pp. 1006-1016.

30. de Genst E., Saerens D., Muyldermans S., Conrath K. Antibody repertoire development in camelids. Dev. Comp. Immunol., 2006, Vol. 30, no. 1-2, pp. 187-198.

31. de Genst E., Silence K., Decanniere K., Conrath K., Loris R., Kinne J., Muyldermans S., Wyns L. Molecular basis for the preferential cleſt recognition by dromedary heavy-chain antibodies. Proc. Natl. Acad. Sci. USA., 2006, Vol. 103, no. 12, pp. 4586-4591.

32. de Groeve K., Deschacht N., de Koninck C., Caveliers V., Lahoutte T., Devoogdt N., Muyldermans S., de Baetselier P., Raes G. Nanobodies as tools for in vivo imaging of specific immune cell types. J. Nucl. Med., 2010, Vol. 51, no. 5, pp. 782-789.

33. de Meyer T., Laukens B., Nolf J., van Lerberge E., de Rycke, R. de Beuckelaer A., de Buck S., Callewaert N., Depicker A. Comparison of VHH-Fc antibody production in Arabidopsis thaliana, Nicotiana benthamiana and Pichia pastoris. Plant Biotechnol. J., 2015, Vol. 13, no. 7, pp. 938-947.

34. de Meyer T., Muyldermans S., Depicker A. Nanobody-based products as research and diagnostic tools. Trends Biotechnol. Elsevier Ltd, 2014, Vol. 32, no. 5, pp. 263-270.

35. Desmyter A., Farenc C., Mahony J., Spinelli S., Bebeacua C., Blangy S. Viral infection modulation and neutralization by camelid nanobodies. PNAS, 2013, Vol. 1, pp. E1371-E1379.

36. Desmyter A., Spinelli S., Payan F., Lauwereys M., Wyns L., Muyldermans S., Cambillau C. Three camelid VHH domains in complex with porcine pancreatic β-amylase: Inhibition and versatility of binding topology. J. Biol. Chem., 2002, Vol. 277, no. 26, pp. 23645-23650.

37. Desmyter A., Transue T. R., Ghahroudi M. A., Thi M. H., Poortmans F., Hamers R., Muyldermans S., Wyns L. Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme. Nat. Struct. Biol., 1996, Vol. 3, no. 9, pp. 803-811.

38. Ding X., Boney-montoya J., Owen B.M., Bookout A.L., Coate C., Mangelsdorf D.J., Kliewer S.A. Nanobody-coupled microbubbles as novel molecular tracer, J. Control Release, 2012, Vol. 158, no. 2, pp. 346-353.

39. Dolk E., van der Vaart M., Hulsik D.L., Vriend G., de Haard H., Spinelli S., Cambillau C., Frenken L., Verrips T. Isolation of llama antibody fragments for prevention of dandruff by phage display in shampoo. Appl. Environ. Microbiol., 2005, Vol. 71, no. 1, pp. 442-450.

40. Dudgeon K., Famm K., Christ D. Sequence determinants of protein aggregation in human VH domains. Protein Eng. Des. Sel., 2009, Vol. 22, no. 3, pp. 217-220.

41. Efimov G.A., Kruglov A.A., Khlopchatnikova Z.V, Rozov F.N., Mokhonov V.V, Rose-John S., Scheller J., Gordon S., Stacey M., Drutskaya M.S., Tillib S.V., Nedospasov S.A. Cell-type-restricted anti-cytokine therapy: TNF inhibition from one pathogenic source. Proc. Natl. Acad. Sci. USA, 2016, Vol. 113, no. 11, pp. 3006-3011.

42. Evazalipour M., D’Huyvetter M., Tehrani B.S., Abolhassani M., Omidfar K., Abdoli S., Arezumand R., Morovvati H., Lahoutte T., Muyldermans S., Devoogdt N. Generation and characterization of nanobodies targeting PSMA for molecular imaging of prostate cancer. Contrast Media Mol. Imaging, 2014, Vol. 9, no. 3, pp. 211-220.

43. Ewert S., Cambillau C., Conrath K., Plückthun A. Biophysical properties of camelid VHH domains compared to those of human VH3 domains. Biochemistry. American Chemical Society, 2002, Vol. 41, no. 11, pp. 3628-3636.

44. Flajnik M.F., Deschacht N., Muyldermans S. A case of convergence: Why did a simple alternative to canonical antibodies arise in Sharks and Camels? PLoS Biol., 2011, Vol. 9, no. 8, p. e1001120.

45. Freeman E.E., Weiss H.A., Glynn J.R., Cross P.L., Whitworth J.A., Hayes R.J. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. England, 2006, Vol. 20, no. 1, pp. 73-83.

46. Frenken L.G., van der Linden R.H., Hermans P.W.J., Bos J.W., Ruuls R.C., de Geus B., Verrips C.T. Isolation of antigen specific Llama VHH antibody fragments and their high level secretion by Saccharomyces cerevisiae. J. Biotechnol., 2000, Vol. 78, no. 1, pp. 11-21.

47. Gainkam L.O.T., Huang L., Caveliers V., Keyaerts M., Hernot S., Vaneycken I., Vanhove C., Revets H., de Baetselier P., Lahoutte T. Comparison of the biodistribution and tumor targeting of two 99mTc-labeled anti-EGFR nanobodies in mice, using pinhole SPECT/micro-CT. J. Nucl. Med. 2008. Vol. 49, no. 5. pp. 788-795.

48. Gainkam T.L.O., Caveliers V., Devoogdt N., Vanhove C., Xavier C., Boerman O., Muyldermans S., Bossuyt A., Lahoutte T. Localization, mechanism and reduction of renal retention of technetium-99m labeled epidermal growth factor receptor-specific nanobody in mice. Contrast Media Mol. Imaging, 2011, Vol. 6, no. 2, pp. 85-92.

49. Gasser M., Waaga-Gasser A.M. Therapeutic Antibodies in Cancer Therapy. Adv. Exp. Med. Biol. United States, 2016, Vol. 917, pp. 95-120.

50. Gennigens C., Collignon J., Jerusalem G., Rorive A, Sautois B. Therapeutic monoclonal antibodies in hematooncology. Rev Med Liege, 2009, Vol. 64, no. 5-6, pp. 264-267.

51. Geoghegan E.M., Zhang H., Desai P.J., Biragyn A., Markham R.B. Antiviral activity of a single-domain antibody immunotoxin binding to glycoprotein D of herpes simplex virus 2. Antimicrob. Agents Chemother, 2015, Vol. 59, no. 1, pp. 527-535.

52. Gherardi E., Birchmeier W., Birchmeier C., Woude G. Vande. Targeting MET in cancer: rationale and progress. Nat. Rev. Cancer. Nature Publishing Group, 2012, Vol. 12, no. 2, pp. 89-103.

53. Greenberg A.S., Avila D., Hughes M., Hughes A., McKinney E.C., Flajnik M.F. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks. Nature, 1995, Vol. 374, no. 6518, pp. 168-173.

54. Hafian H., Sukhanova A., Turini M., Chames P., Baty D., Pluot M., Cohen J.H.M., Nabiev I., Millot J.M. Multiphoton imaging of tumor biomarkers with conjugates of single-domain antibodies and quantum dots. Nanomedicine Nanotechnology, Biol. Med. Elsevier Inc., 2014, Vol. 10, no. 8, pp. 1701-1709.

55. Hamers-Casterman C., Atarhouch T., Muyldermans S., Robinson G., Hamers C., Songa E.B., Bendahman N., Hamers R. Naturally occurring antibodies devoid of light chains. Nature, 1993, Vol. 363, no. 6428, pp. 446-448.

56. Harmsen M.M., de Haard H.J. Properties, production, and applications of camelid single-domain antibody fragments. Appl. Microbiol. Biotechnol, 2007, Vol. 77, no. 1, pp. 13-22.

57. Harmsen M.M., Fijten H.P.D., Engel B., Dekker A., Eblé P.L. Passive immunization with llama single-domain antibody fragments reduces foot-and-mouth disease transmission between pigs. Vaccine, 2009, Vol. 27, no. 13, pp. 1904-1911.

58. Harmsen M.M., van Solt C.B., van Zijderveld-Van Bemmel A.M., Niewold T.A., van Zijderveld F.G. Selection and optimization of proteolytically stable llama single-domain antibody fragments for oral immunotherapy. Appl. Microbiol. Biotechnol., 2006, Vol. 72, no. 3, pp. 544-551.

59. Hassanzadeh-Ghassabeh G., Devoogdt N., de Pauw P., Vincke C., Muyldermans S. Nanobodies and their potential applications. Nanomedicine, 2013, Vol. 8, no. 6, pp. 1013-1026.

60. Helma J., Cardoso M. C., Muyldermans S., Leonhardt H. Nanobodies and recombinant binders in cell biology. J. Cell Biol, 2015, Vol. 209, no. 5, pp. 633-644.

61. Herrera C., Tremblay J.M., Shoemaker C.B., Mantis N.J. Mechanisms of ricin toxin neutralization revealed through engineered homodimeric and heterodimeric camelid antibodies. J. Biol. Chem. United States, 2015, Vol. 290, no. 46, pp. 27880-27889.

62. Heukers R., van Bergen en Henegouwen P.M.P., Oliveira S. Nanobody-photosensitizer conjugates for targeted photodynamic therapy. Nanomedicine Nanotechnology, Biol. Med. Elsevier Inc., 2014, Vol. 10, no. 7, pp. 1441-1451.

63. Hmila I., Abdallah R.B.A.-B., Saerens D., Benlasfar Z., Conrath K., Ayeb M.E., Muyldermans S., Bouhaouala-Zahar B. VHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI’. Mol. Immunol. England, 2008, Vol. 45, no. 14, pp. 3847-3856.

64. Hmila I., Cosyns B., Tounsi H., Roosens B., Caveliers V., Abderrazek R. Ben, Boubaker S., Muyldermans S., Ayeb M.E., Bouhaouala-Zahar B., Lahoutte T. Pre-clinical studies of toxin-specific Nanobodies: Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming. Toxicol. Appl. Pharmacol. Elsevier Inc., 2012, Vol. 264, no. 2, pp. 222-231.

65. Hoefman S., Ottevaere I., Baumeister J., Sargentini-Maier M. Pre-clinical intravenous serum pharmacokinetics of albumin binding and non-half-life extended Nanobodies®. Antibodies, 2015, Vol. 4, no. 3, pp. 141-156.

66. Hudson P.J., Souriau C. Engineered antibodies. Nat. Med., 2003, Vol. 9, no. 1, pp. 129-134.

67. Hultberg A., Temperton N.J., Rosseels V., Koenders M., Gonzalez-Pajuelo M., Schepens B., Ibañez L.I., Vanlandschoot P., Schillemans J., Saunders M., Weiss R.A., Saelens X., Melero J.A., Verrips C.T., Van Gucht S., De Haard H.J. Llama-derived single domain antibodies to build multivalent, superpotent and broadened neutralizing anti-viral molecules. PLoS One, 2011, Vol. 6, no. 4, p. e17665.

68. Hultberg A., Tremblay D. M., de Haard H., Verrips T., Moineau S., Hammarstrom L., Marcotte H. Lactobacillli expressing llama VHH fragments neutralise Lactococcus phage. BMC Biotechnol., 2007, Vol. 7, no. 58, pp. 7-58.

69. Ibañez L. I., de Filette M., Hultberg A., Verrips T., Temperton N., Weiss R.A., Vandevelde W., Schepens B., Vanlandschoot P., Saelens X. Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. J. Infect. Dis., 2011, Vol. 203, no. 8, pp. 1063-1072.

70. Jähnichen S., Blanchetot C., Maussang D., Gonzalez-Pajuelo M., Chow K.Y., Bosch L., de Vrieze S., Serruys B., Ulrichts H., Vandevelde W., Saunders M., de Haard H.J., Schols D., Leurs R., Vanlandschoot P., Verrips T., Smit M.J. CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells. Proc. Natl. Acad. Sci. USA. 2010, Vol. 107, no. 47, pp. 20565-20570.

71. Kandalaſt H., Hussack G., Aubry A., van Faassen H., Guan Y., Arbabi-Ghahroudi M., MacKenzie R., Logan S.M., Tanha J. Targeting surface-layer proteins with single-domain antibodies: a potential therapeutic approach against Clostridium difficile-associated disease. Appl. Microbiol. Biotechnol., 2015, Vol. 99, no. 20, pp. 8549-8562.

72. Kijanka M., Dorresteijn B., Oliveira S., van Bergen en Henegouwen P.M.P. Nanobody-based cancer therapy of solid tumors. Nanomedicine, 2015, Vol. 10, no. 1, pp. 161-174.

73. Kijanka M., Warnders F.J., El Khattabi M., Lub-De Hooge M., van Dam G.M., Ntziachristos V., De Vries L., Oliveira S., van Bergen En Henegouwen P.M.P. Rapid optical imaging of human breast tumour xenograſts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery. Eur. J. Nucl. Med. Mol. Imaging, 2013, Vol. 40, no. 11, pp. 1718-1729.

74. Kirchhofer A., Helma J., Schmidthals K., Frauer C., Cui S., Karcher A., Pellis M., Muyldermans S., Casas-Delucchi C.S., Cardoso M.C., Leonhardt H., Hopfner K.-P., Rothbauer U. Modulation of protein properties in living cells using nanobodies. Nat. Struct. Mol. Biol. Nature Publishing Group, 2010, Vol. 17, no. 1, pp. 133-138.

75. Kratz F., Elsadek B. Clinical impact of serum proteins on drug delivery. J. Control. Release. Netherlands, 2012, Vol. 161, no. 2, pp. 429-445.

76. Lafaye P., Achour I., England P., Duyckaerts C., Rougeon F. Single-domain antibodies recognize selectively small oligomeric forms of amyloid beta, prevent Abeta-induced neurotoxicity and inhibit fibril formation. Mol. Immunol., 2009, Vol. 46, no. 4, pp. 695-704.

77. Li A., Xing J., Li L., Zhou C., Dong B., He P., Li Q, Wang Z. A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells. AMB Express, 2016, Vol. 6, no. 1, p. 32.

78. Maier J., Traenkle B., Rothbauer U. Real-time analysis of epithelial-mesenchymal transition using fluorescent single-domain antibodies. Sci. Rep. Nature Publishing Group, 2015, Vol. 5, p. 13402.

79. Maussang D., Mujić-Delić A., Descamps F.J., Stortelers C., Vanlandschoot P., Stigter-van Walsum M., Vischer H.F., van Roy M., Vosjan M., Gonzalez-Pajuelo M., van Dongen G.A.M.S., Merchiers P., van Rompaey P. Llama-derived single variable domains (nanobodies) directed against chemokine receptor CXCR7 reduce head and neck cancer cell growth in vivo. J. Biol. Chem., USA, 2013, Vol. 288, no. 41, pp. 29562-29572.

80. Mccoy L.E., Groppelli E., Blanchetot C., Haard H.D., Verrips T., Rutten L., Weiss R.A., Jolly C. Neutralisation of HIV-1 cell-cell spread by human and llama antibodies. Retrovirology, 2014, Vol. 11, no. 83, pp. 1-15.

81. Miao Z., Luker K.E., Summers B.C., Berahovich R., Bhojani M.S., Rehemtulla A., Kleer C.G., Essner J.J., Nasevicius A., Luker G.D., Howard M.C., Schall T.J. CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc. Natl. Acad. Sci. USA. 2007, Vol. 104, no. 40, pp. 15735-15740.

82. Moutel S., Perez F. Utilisation des intrabodies: de l’étude des protéines intracellulaires à l’ immunisation thérapeutique. Medecine/Sciences, 2009, Vol. 25, pp. 1173-1176.

83. Movahedi K., Schoonooghe S., Laoui D., Houbracken I., Waelput W., Breckpot K., Bouwens L., Lahoutte T., de Baetselier P., Raes G., Devoogdt N., van Ginderachter J.A. Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages. Cancer Res., 2012, Vol. 72, no. 16, pp. 4165-4177.

84. Mujić-Delić A., de Wit R.H., Verkaar F., Smit M.J. GPCR-targeting nanobodies: Attractive research tools, diagnostics, and therapeutics. Trends Pharmacol. Sci., 2014, Vol. 35, no. 5, pp. 247-255.

85. Muyldermans S. Nanobodies: natural single-domain antibodies. Annu. Rev. Biochem., 2013, Vol. 82, pp. 775-797.

86. Olichon A., Surrey T. Selection of genetically encoded fluorescent single domain antibodies engineered for efficient expression in Escherichia coli. J. Biol. Chem., 2007, Vol. 282, no. 50, pp. 36314-36320.

87. Pant N., Hultberg A., Zhao Y., Svensson L., Pan-Hammarstrom Q., Johansen K., Pouwels P.H., Ruggeri F.M., Hermans P., Frenken L. Boren T., Marcotte H., Hammarstrom L. Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea. J. Infect. Dis., 2006, Vol. 194, no. 11, pp. 1580-1588.

88. Panza P., Maier J., Schmees C., Rothbauer U., Söllner C. Live imaging of endogenous protein dynamics in zebrafish using chromobodies. Development. The Company of Biologists, 2015, Vol. 142, no. 10, pp. 1879-1884.

89. Peyvandi F., Scully M., Kremer Hovinga J.A., Cataland S., Knöb P., Wu H., Artoni A., Westwood J.-P., Mansouri Taleghani M., Jilma B., Callewaert F., Ulrichts H., Duby C., Tersago D. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N. Engl. J. Med., 2016, Vol. 374, no. 6, pp. 511-522.

90. Platonova E., Winterflood C.M., Junemann A., Albrecht D., Faix J., Ewers, H. Single-molecule microscopy of molecules tagged with GFP or RFP derivatives in mammalian cells using nanobody binders. Methods. Elsevier Inc., 2015, Vol. 88, pp. 89-97.

91. Power U.F., Stortelers C., Allosery K., Melero J.A. Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection. Antimicrob. Agents Chemother., 2016, Vol. 60, no. 1, pp. 6-13.

92. Pruszynskia M., Koumarianoua E., Vaidyanathana G., Revetsc H., Devoogdtd N., Lahoutted T., Zalutsky M.R. Targeting breast carcinoma with radioiodinated anti-HER2 Nanobody. Nucl. Med. Biol., 2013, Vol. 40, no. 1, pp. 52-59.

93. Put S., Schoonooghe S., Devoogdt N., Schurgers E., Avau A., Mitera T., D’Huyvetter M., De Baetselier P., Raes G., Lahoutte T., Matthys P. SPECT imaging of joint inflammation with Nanobodies targeting the macrophage mannose receptor in a mouse model for rheumatoid arthritis. J. Nucl. Med., 2013, Vol. 54, no. 5, pp. 807-814.

94. Pysz M.A., Gambhir S.S., Willmann J.K. Molecular imaging: current status and emerging strategies. Clin. Radiol., 2010, Vol. 65, no. 7, pp. 500–516.

95. Rajabi-Memari H., Jalali-Javaran M., Rasaee M.J., Rahbarizadeh F., Forouzandeh-Moghadam M., Esmaili A. Expression and characterization of a recombinant single-domain monoclonal antibody against MUC1 mucin in tobacco plants. Hybridoma (Larchmt). United States, 2006, Vol. 25, no. 4. pp. 209-215.

96. Rakovich T.Y., Mahfoud O.K., Mohamed B.M., Prina-Mello A., Crosbie-Staunton K., van den Broeck T., de Kimpe L., Sukhanova A., Baty D., Rakovich A., Maier S.A., Alves F., Nauwelaers F., Nabiev I., Chames P., Volkov Y. Highly sensitive single domain antibody-quantum dot conjugates for detection of HER2 biomarker in lung and breast cancer cells. ACS Nano. United States, 2014, Vol. 8, no. 6, pp. 5682-5695.

97. Rashidian M., Keliher E.J., Bilate A.M., Duarte J.N., Wojtkiewicz G.R., Jacobsen J.T., D’Huyvette Cragnolini J., Swee L.K., Victora G.D., Weissleder R.., Ploegh H. L. Noninvasive imaging of immune responses. Proc. Natl. Acad. Sci. USA, 2015, Vol. 112, no. 19, pp. 6146-6151.

98. Roovers R.C., Laeremans T., Huang L., De Taeye S., Verkleij A.J., Revets H., de Haard H.J., van Bergen En Henegouwen P.M.P. Efficient inhibition of EGFR signalling and of tumour growth by antagonistic anti-EGFR Nanobodies. Cancer Immunol. Immunother., 2007, Vol. 56, no. 3, pp. 303–317.

99. Rothbauer U., Zolghadr K., Tillib S., Nowak D., Schermelleh L., Gahl A., Backmann N., Conrath K., Muyldermans S., Cardoso C., Leonhardt H. Targeting and tracing antigens in live cells with fluorescent nanobodies. Nat. Meth., 2006, Vol. 3, no. 11, pp. 887-889.

100. Rutgers K.S., Nabuurs R.J.A., van den Berg S.A.A., Schenk G.J., Rotman M., Verrips C.T., van Duinen S.G., Maat-Schieman M.L., van Buchem M.A., de Boer A.G., van der Maarel S.M. Transmigration of beta amyloid specific heavy chain antibody fragments across the in vitro blood-brain barrier. Neuroscience. Elsevier Inc., 2011, Vol. 190, pp. 37-42.

101. Sadeqzadeh E., Rahbarizadeh F., Ahmadvand D., Rasaee M.J., Parhamifar L., Moghimi S.M. Combined MUC1-specific nanobody-tagged PEG-polyethylenimine polyplex targeting and transcriptional targeting of tBid transgene for directed killing of MUC1 over-expressing tumour cells. J. Control. Release. Elsevier B.V., 2011, Vol. 156, no. 1, pp. 89-95.

102. Saerens D., Muyldermans S. Single domain antibodies: methods and protocols. Methods Mol. Biol., 2012, Vol. 911, pp. 277-286.

103. Sawyer L.A. Antibodies for the prevention and treatment of viral diseases. Antiviral Res., 2000, Vol. 47, no. 2, pp. 57-77.

104. Schorpp K., Rothenaigner I., Maier J., Traenkle B., Rothbauer U., Hadian K. A multiplexed high-content screening approach using the chromobody technology to identify cell cycle modulators in living cells. J. Biomol. Screen, 2016, Vol. 1, no. 13.

105. Sherwood L.J., Osborn L.E., Carrion Jr.R., Patterson J.L., Hayhurst A. Rapid assembly of sensitive antigen-capture assays for Marburg virus, using in vitro selection of llama single-domain antibodies, at biosafety level 4.

106. J. Infect. Dis., 2007, Vol. 196, no. s2, pp. S213-S219.

107. Siontorou C.G. Nanobodies as novel agents for disease diagnosis and therapy. Int. J. Nanomedicine, 2013, Vol. 8,

108. pp. 4215-4227.

109. Soukos N.S., Hamblin M.R., Keel S., Fabian R.L., Deutsch T.F., Hasan T. Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo. Cancer Res., 2001, Vol. 61, no. 11, pp. 4490-4496.

110. Spinelli S., Frenken L.G., Hermans P., Verrips T., Brown K., Tegoni M., Cambillau C. Camelid heavy-chain variable domains provide efficient combining sites to haptens. Biochemistry. United States, 2000, Vol. 39, no. 6, pp. 1217-1222.

111. Sukhanova A., Even-Desrumeaux K., Kisserli A., Tabary T., Reveil B., Millot J. M., Chames P., Baty D., Artemyev M., Oleinikov V., Pluot M., Cohen J.H.M., Nabiev I. Oriented conjugates of single-domain antibodies and quantum dots: Toward a new generation of ultrasmall diagnostic nanoprobes. Nanomedicine Nanotechnology, Biol. Med. Elsevier Inc., 2012, Vol. 8, no. 4, pp. 516-525.

112. Thys B., Saerens D., Schotte L., de Bleeser G., Muyldermans, S., Hassanzadeh-Ghassabeh G., Rombaut B. A simple quantitative affinity capturing assay of poliovirus antigens and subviral particles by single-domain antibodies using magnetic beads. J. Virol. Methods. Elsevier B.V., 2011, Vol. 173, no. 2, pp. 300-305.

113. Tillib S.V., Ivanova T.I., Vasilev L.A., Rutovskaya M.V., Saakyan S.A., Gribova I.Y., Tutykhina I.L., Sedova E.S., Lysenko A.A., Shmarov M.M., Logunov D.Y., Naroditsky B.S., Gintsburg A.L. Formatted single-domain antibodies can protect mice against infection with influenza virus (H5N2). Antiviral Res., 2013, Vol. 97, no. 3, pp. 245-254.

114. Torres T., Romanelli M, Chiricozzi A. A revolutionary therapeutic approach for psoriasis: bispecific biological agents. Expert Opinion on Investigational Drugs, 2016, Vol. 25, Iss. 7.

115. Ulrichts H., Silence K., Schoolmeester A., de Jaegere P., Rossenu S., Roodt J., Priem S., Lauwereys M., Casteels P., van Bockstaele F., Verschueren, Stanssens K., Baumeister P., Holz J., Beate J. Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs. Blood, 2011, Vol. 118, no. 3, pp. 757-765.

116. Unger M., Eichhoff A. M., Schumacher L., Strysio M., Menzel S., Schwan C., Alzogaray V., Zylberman V., Seman M., Brandner J. Rohde H., Zhu K., Haag F. Mittrücker H.-W., Goldbaum F., Aktories K., Koch-Nolte F. Selection of nanobodies that block the enzymatic and cytotoxic activities of the binary Clostridium difficile toxin CDT. Sci. Rep., 2015, Vol. 5, p. 7850.

117. van Bockstaele F., Holz J.-B., Revets H. The development of nanobodies for therapeutic applications. Curr. Opin. Investig. Drugs. England, 2009, Vol. 10, no. 11, pp. 1212-1224.

118. van der Vaart J.M., Pant N., Wolvers D., Bezemer S., Hermans P.W., Bellamy K., Sarker S.A., van der Logt C.P.E., Svensson L., Verrips C.T., Hammarstrom L., van Klinken B.J.W. Reduction in morbidity of rotavirus

119. induced diarrhoea in mice by yeast produced monovalent llama-derived antibody fragments. Vaccine, 2006, Vol. 24, no. 19, pp. 4130-4137.

120. van Driel P.B.A.A., Boonstra M.C., Slooter M.D., Heukers R., Stammes M.A., Snoeks T.J.A., de Bruijn H.S., van Diest P.J., Vahrmeijer A.L., van Bergen en Henegouwen P.M.P., van de Velde C.J.H., Löwik C.V.G.M., Robinson D.J., Oliveira S. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer. J. Control. Release, 2016, Vol. 229, pp. 93-105.

121. van Driel P.B.A.A., van der Vorst J.R., Verbeek F.P.R., Oliveira S., Snoeks T.J.A., Keereweer S., Chan B., Boonstra M.C., Frangioni J.V., van Bergen en Henegouwen P.M.P., Vahrmeijer A.L., Lowik C.W.G.M. Intraoperative fluorescence delineation of head and neck cancer with a fluorescent Anti-epidermal growth factor receptor nanobody. Int. J. Cancer, 2014, Vol. 134, no. 11, pp. 2663-2673.

122. van Heeke G., Allosery K., de Brabandere V., de Smedt T., Detalle L., de Fougerolles A. Nanobodies® as inhaled biotherapeutics for lung diseases. Pharmacol. Ther., 2016, JPT-06924.

123. van Roy M., Ververken C., Beirnaert E., Hoefman S., Kolkman J., Vierboom M., Breedveld E., ’t Hart B., Poelmans S., Bontinck L., Hemeryck A., Jacobs S.,Baumeister J., Ulrichts H. The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis. Arthritis Research and Therapy, 2015, Vol. 17, p. 135.

124. Vaneycken I., Devoogdt N., van Gassen N., Vincke C., Xavier C., Wernery U., Muyldermans S., Lahoutte T., Caveliers V. Preclinical screening of anti-HER2 nanobodies for molecular imaging of breast cancer. FASEB J., 2011, Vol. 25, no. 7, pp. 2433-2446.

125. Vanlandschoot P., Stortelers C., Beirnaert E., Itatí L., Schepens B., Depla E., Saelens X. Nanobodies: New ammunition to battle viruses. Antiviral Research, 2011, Vol. 92, pp. 389-407.

126. Vercruysse T., Pardon E., Vanstreels E., Steyaert J., Daelemans D. An intrabody based on a llama single-domain antibody targeting the N-terminal α-helical multimerization domain of HIV-1 rev prevents viral production. J. Biol. Chem. USA, 2010, Vol. 285, no. 28, pp. 21768-21780.

127. Vosjan M.J., Vercammen J., Kolkman J.A., Stigter-van Walsum M., Revets H., van Dongen G.A. Nanobodies Targeting the hepatocyte growth factor: potential new drugs for molecular cancer therapy. Mol. Cancer Ther., 2012, Vol. 11, no. 4, pp. 1017-1025.

128. Wesolowski J., Alzogaray V., Reyelt J., Unger M., Juarez K., Urrutia M., Cauerhff A., Danquah W., Rissiek B., Scheuplein F., Schwarz N., Adriouch S., Boyer O., Seman M., Licea A., Serreze D. V., Goldbaum F. A., Haag F., Koch-Nolte F. Single domain antibodies: Promising experimental and therapeutic tools in infection and immunity. Med. Microbiol. Immunol., 2009, Vol. 198, no. 3, pp. 157-174.

129. Yardehnavi N., Behdani M., Bagheri K.P., Mahmoodzadeh A., Khanahmad H., Shahbazzadeh D., Habibi-Anbouhi M., Ghassabeh G.H., Muyldermans S.A. Сamelid antibody candidate for development of a therapeutic agent against Hemiscorpius lepturus envenomation. FASEB J., 2014, Vol. 28, no. 9, pp. 4004-4014.


Для цитирования:


Горшкова Е.Н., Василенко В.А., Тиллиб С.В., Астраханцева И.В. ОДНОДОМЕННЫЕ АНТИТЕЛА И БИОИНЖЕНЕРНЫЕ ПРЕПАРАТЫ НА ИХ ОСНОВЕ: НОВЫЕ ВОЗМОЖНОСТИ ДЛЯ ДИАГНОСТИКИ И ТЕРАПИИ. Медицинская иммунология. 2016;18(6):505-520. https://doi.org/10.15789/1563-0625-2016-6-505-520

For citation:


Gorshkova E.N., Vasilenko E.A., Tillib S.V., Astrakhantseva I.V. SINGLE DOMAIN ANTIBODIES AND BIOENGINEERING DRUGS ON THEIR BASIS: NEW OPPORTUNITIES FOR DIAGNOSTICS AND THERAPY. Medical Immunology (Russia). 2016;18(6):505-520. (In Russ.) https://doi.org/10.15789/1563-0625-2016-6-505-520

Просмотров: 492


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1563-0625 (Print)
ISSN 2313-741X (Online)