Preview

Proceedings of the National Academy of Sciences of Belarus, Biological Series

Advanced search

CpG OLIGODEOXYNUCLEOTIDES AND THEIR PRACTICAL USAGE

Abstract

Bacterial DNA (including plasmids) and synthetic oligo-2ʹ-deoxynucleotides containing non-methylated CpGdinucleotides (CpG-ODN) upon introduction into human or animal body stimulate both innate and adaptive immune responses. In this regard bright prospects open up for therapeutic application of CpG-ODN to cope with infectious, allergic diseases and cancer. However, CpG-ODN molecules are negatively charged and hence can hardly penetrate through cell membrane bearing the equipolar surface charge. Moreover, native CpG-ODN are easily cleaved by nucleases. One of the effective methods to counter CpG-ODN nuclease attack is chemical modification of their sugar-phosphate skeleton. Yet some cases have been reported when supply of modified molecules caused grave side-effects. All these circumstances restrain considerably therapeutic prospects of CpG-ODN and spur-up the interest in search of efficient systems for CpG-ODN delivery to target tissues and cells. Lately progress of nanobiotechnologies provided unprecedented opportunities for encapsulation of active drug substances (including CpG-ODN) into various nanosize transport vehicles and synthesis of multiform nanostructures from CpG-ODN. The use of such delivery systems raises significantly both CpG-ODN stability and extent of their internalization into target cells. It is plausible that development of nanotransporters will enable to get rid of chemical CpG-ODN modification provoking adverse effects. 

About the Authors

A. I. Zinchenko
Institute of Microbiology of the National Academy of Sciences of Belarus, Minsk
Belarus

Corresponding Member, D. Sc. (Biol.), Professor, Head of the Laboratory

2, Kuprevich Str., 220141



A. S. Shchokolova
Institute of Microbiology of the National Academy of Sciences of Belarus, Minsk
Belarus

Ph. D. (Biol.), Senior researcher

2, Kuprevich Str., 220141



References

1. Medzhitov R., Janeway C. A. Innate immunity: the virtues of a nonclonal system of recognition. Cell, 1997, vol. 91, pp. 295–298.

2. Janeway C. A., Medzhitov R. Innate immune recognition. Annual Review of Immunology, 2002, vol. 20, pp. 197–216. DOI: 10.1146/annurev.immunol.20.083001.084359

3. Aderem A., Ulevitch R. J. Toll-like receptors in the induction of the innate immune response. Nature, 2000, vol. 406, pp. 782–787.

4. Hobohm U., Stanford J. L., Grange J. M. Pathogen-associated molecular pattern in cancer immunotherapy. Critical Review of Immunology, 2008, vol. 28, no. 2, pp. 95–107.

5. Oth T., Vanderlocht J., Van Elssen C. H., Bos G. M., Germeraad W. T. Pathogen-associated molecular patterns induced crosstalk between dendritic cells, T helper cells, and natural killer helper cells can improve dendritic cell vaccination. Mediators of Inflammation, 2016, vol. 2016: 5740373. DOI: 10.1155/2016/5740373

6. Krieg A. M., Yi A. K., Matson S., Waldschmidt T. J., Bishop G. A., Teasdale R., Koretzky G. A., Klinman D. M. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature, 1995, vol. 374, pp. 546–549. DOI: 10.1038/374546a0

7. Krieg A. M. Therapeutic potential of toll-like receptor 9 activation. Nature Review Drug Discovery, 2006, vol. 5, pp. 471–484. DOI: 10.1038/nrd2059

8. Krieg A. M. Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides. Biochimica et Biophysica Acta (BBA) – Gene Structure and Expression, 1999, vol. 1489, pp. 107–116.

9. Jain V. V., Kitagaki K., Kline J. N. CpG DNA and immunotherapy of allergic airway diseases. Clinical and Experimental Allergy, 2003, vol. 33, no. 10, pp. 1330–1335. DOI: 10.1046/j.1365-2222.2003.01763.x

10. Bauer S., Kirschning C. J., Hacker H., Redecke V., Hausmann S., Akira S., Wagner H., Lipford G. B. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proceedings of the National Academy of Sciences of the United States of America, 2001, vol. 98, no. 16, pp. 9237–9242. DOI: 10.1073/pnas.161293498

11. Krieg A. M. CpG motifs in bacterial DNA and their immune effects. Annual Review of Immunology, 2002, vol. 20, pp. 709–760. DOI: 10.1146/annurev.immunol.20.100301.064842

12. Klinman D. M. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nature Reviews. Immunology, 2004, vol. 4, no. 4, pp. 249–258. DOI: 10.1038/nri1329

13. Wilson H. L., Dar A., Napper S. K., Marianela Lopez A., Babiuk L. A., Mutwiri G. K. Immune mechanisms and therapeutic potential of CpG oligodeoxynucleotides. International Review of Immunology, 2006, vol. 25, no. 3/4, pp. 183–213. DOI: 10.1080/08830180600785868

14. Stacey K. J., Sweet M. J., Hume D. A. Macrophages ingest and are activated by bacterial DNA. Journal of Immunology, 1996, vol. 157, no. 5, pp. 2116–2122.

15. Sun S. Q., Zhang X., Tough D., Sprent J. Type I interferon-mediated stimulation of T cells by CpG DNA. Journal of Experimental Medicine, 1998, vol. 188, pp. 2335–2342.

16. Fonseca D. E., Kline J. N. Use of CpG oligodeoxynucleotides in treatment of asthma and allergic disease. Advances of Drug Delivery. Reviews, 2009, vol. 61, pp. P. 256–262.

17. Klinman D. M., Klaschik S., Sato T., Tross D. CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases. Advanced Drug Delivery Reviews, 2009, vol. 61, no. 3, pp. 248–255. DOI: 10.1016/j.addr.2008.12.012

18. Murad Y. M., Clay T. M. CpG oligodeoxynucleotides as TLR9 agonists: therapeutic applications in cancer. BioDrugs, 2009, vol. 23, no. 6, pp. 361–375. DOI: 10.2165/11316930-000000000-00000

19. Hacker H., Mischak H., Miethke T., Liptay S., Schmid R., Sparwasser T., Heeg K., Lipford G. B., Wagner H. CpGDNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. The EMBO Journal, 1998, vol. 17, no. 21, pp. 6230–6240. DOI: 10.1093/emboj/17.21.6230

20. Rutz M., Metzger J., Gellert T., Luppa P., Lipford G. B., Wagner H., Bauer S. Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. European Journal of Immunology, 2004, vol. 34, no. 9, pp. 2541–2550. DOI: 10.1002/eji.200425218

21. Yi A. K., Klinman D. M., Martin T. L., Matson S., Krieg A. M. Rapid immune activation by CpG motifs in bacterial DNA: systemic induction of IL-6 transcription through an antioxidant-sensitive pathway. Journal of Immunology, 1996, vol. 157, no. 12, pp. 5394–5402.

22. Redford T. W., Yi A. K., Ward C. T., Krieg A. M. Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides. Journal of Immunology, 1998, vol. 161, no. 8, pp. 3930–3935.

23. Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity. Cell, 2006, vol. 124, no. 4, pp. 783–801. DOI: 10.1016/j.cell.2006.02.015

24. Jung J., Yi A. K., Zhang X., Choe J., Li L., Choi Y. S. Distinct response of human B cell subpopulations in recognition of an innate immune signal, CpG DNA. Journal of Immunology, 2002, vol. 169, no. 5, pp. 2368–2373.

25. Bernasconi N. L., Traggiai E., Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science, 2002, vol. 298, pp. 2199–2202. DOI: 10.1126/science.1076071

26. Asselin-Paturel C., Brizard G., Chemin K., Boonstra A., O’Garra, A., Vicari A., Trinchieri G. Type I interferon dependence of plasmacytoid dendritic cell activa-tion and migration. Journal of Experimental Medicines, 2005, vol. 201, no. 7, pp. 1157–1167. DOI: 10.1084/jem.20041930

27. Vollmer J., Jurk M., Samulowitz U., Lipford G., Forsbach A., Wüllner M., Tluk S., Hartmann H., Kritzler A., Müller C., Schetter C., Krieg A. M. CpG oligodeoxynucleotides stimulate IFN-gamma-inducible protein-10 production in human B cells. Journal of Endotoxin Research, 2004, vol. 10, no. 6, pp. 431–438. DOI: 10.1179/096805104225006534

28. Napolitani G., Rinaldi A., Bertoni F., Sallusto F., Lanzavecchia A. Selected TLR agonist combinations synergistically trigger a TH1 polarizing program in dendritic cells. Nature. Immunology, 2005, vol. 6, no. 8, pp. 769–776.

29. Klinman D. M. Use of CpG oligodeoxynucleotides as immunoprotective agents. Expert Opinion on Biological Therapy, 2004, vol. 4, no. 6, pp. 937–946. DOI: 10.1517/14712598.4.6.937

30. Klinman D. M., Currie D., Gursel I., Verthelyi D. Use of CpG oligodeoxynucleotides as immune adjuvants. Immunological Reviews, 2004, vol. 199, pp. 201–216. DOI: 10.1111/j.0105-2896.2004.00148.x

31. Zhao B. G., Vasilakos J. P., Tross D., Smirnov D., Klinman D. M. Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors. Journal for Immunotherapy of Cancer, 2014, vol. 2. Available at: http://www.immunotherapyofcancer.org/content/2/1/12 (accessed 15.06.2017).

32. Carpentier A. F., Auf G., Delattre J. Y. CpG-oligonucleotides for cancer immunotherapy: review of the literature and potential applications in malignant glioma. Frontiers in Bioscience, 2003, vol. 8, pp. 115–127.

33. Tokunaga T., Yamamoto T., Yamamoto S. How BCG led to the discovery of immunostimulatory DNA. Japan Journal of Infection Diseases, 1999, vol. 52, no. 1, pp. 1–11.

34. Krieg A. M. CpG motifs: the active ingredient in bacterial extracts? Nature Medicine, 2003, vol. 9, no. 7, pp. 831–835. DOI: 10.1038/nm0703-831

35. Sands H., Gorey-Feret L. J., Ho S. P., Bao Y., Cocuzza A. J., Chidester D., Hobbs F.W. Biodistribution and metabolism of internally H-3 labeled oligonucleotides. II. 3ʹ,5ʹ-blocked oligonucleotides. Molecular Pharmacology, 1995, vol. 47, pp. 636–646.

36. Agrawal S., Zhao Q. Y. Antisense therapeutics. Current Opinion in Chemical Biology, 1998, vol. 2, no. 4, pp. 519–528.

37. Meng W., Yamazaki T., Nishida Y., Hanagata N. Nuclease-resistant immunostimulatory phosphodiester CpG oligodeoxynucleotides as human toll-like receptor 9 agonists. BMC Biotechnology, 2011, vol. 11. DOI: 10.1186/1472-6750-11-88

38. Zhang H., Gao X. D. Nanodelivery systems for enhancing the immunostimulatory effect of CpG oligodeoxynucleotides. Materials Science and Engineering: C, 2017, vol. 70, pt. 2, pp. 935–946.

39. Zhu Y., Meng W., Li X., Gao H., Hanagata N. Design of mesoporous silica/cytosine‒phosphodiester‒guanine oligodeoxynucleotide complexes to enhance delivery efficiency. Journal of Physical Chemistry, 2011, vol. 115, no. 2, pp. 447–452. DOI: 10.1021/jp109535d

40. Zhi C., Meng W., Yamazaki T., Bando Y., Golberg D., Tang C., Hanagata N. BN nanospheres as CpG ODN carriers for activation of toll-like receptor 9. Journal of Materials Chemistry, 2011, vol. 21, no. 14, pp. 5219–5222.

41. Ahlers J. D., Belyakov I. M., Berzofsky J. A. Cytokine, chemokine, and costimulatory molecule modulation to enhance efficacy of HIV vaccines. Current Molecular Medicine, 2003, vol. 3, no. 3, pp. 285–301.

42. Nichani A. K., Kaushik R. S., Mena A., Popowych Y., Dent D., Townsend H. G., Mutwiri G., Hecker R., Babiuk L. A., Griebel P. J. CpG oligodeoxynucleotide induction of antiviral effector molecules in sheep. Cellular Immunology, 2004, vol. 227, no. 1, pp. 24–37. DOI: 10.1016/j.cellimm.2004.01.004

43. Fuchs S., Klier J., May A., Winter G., Coester C., Gehlen H. Towards an inhalative in vivo application of immunomodulating gelatin nanoparticles in horse-related preformulation studies. Journal of Microencapsulation, 2012, vol. 29, no. 7, pp. 615–625.

44. Kwong B., Liu H., Irvine D. J. Induction of potent anti-tumor responses while eliminating systemic side effects via liposomeanchored combinatorial immunotherapy. Biomaterials, 2011, vol. 32, pp. 5134–5147. DOI: 10.1016/j.biomaterials.2011.03.067.

45. Andrews C. D., Huh M. S., Patton K., Higgins D., Van Nest G., Ott G., Lee K. D. Encapsulating immunostimulatory CpG oligonucleotides in Listeriolysin O-liposomes promotes a Th1-type response and CTL activity. Molecular Pharmaceutics, 2012, vol. 9, no. 5, pp. 1118–1125. DOI: 10.1021/mp2003835

46. Zhou S., Hashida Y., Kawakami S., Mihara J., Umeyama T., Imahori H., Murakami T., Yamashita F., Hashida M. Preparation of immunostimulatory single-walled carbon nanotube/CpG DNA complexes and evaluation of their potential in cancer immunotherapy. International Journal of Pharmaceutics, 2014, vol. 471, no. 1/2, pp. 214–223. DOI: 10.1016/j.ijpharm.2014.05.037

47. Sun J., Chao J., Huang J., Yin M., Zhang H., Peng C., Zhong Z., Chen N. Uniform small graphene oxide as an efficient cellular nanocarrier for immunostimulatory CpG oligonucleotides. ACS Applied Materials and Interfaces, 2014, vol. 6, no. 10, pp. 7926–7932. DOI: 10.1021/am5012595

48. Lin A. Y., Almeida J. P., Bear A., Liu N., Luo L., Foster A. E., Drezek R. A. Gold nanoparticle delivery of modified CpG stimulates macrophages and inhibits tumor growth for enhanced immunotherapy. PLoS One, 2013, vol. 8, no. 5, e63550.

49. Tao W., Ziemer K. S., Gill H. S. Gold nanoparticle-M2e conjugate coformulated with CpG induces protective immunity against influenza A virus. Nanomedicine, 2014, vol. 9, no. 2, pp. 237‒252. DOI: 10.2217/nnm.13.58

50. Chen N., Wei M., Sun Y., Li F., Pei H., Li X., Su S., He Y., Wang L., Shi J., Fan C., Huang Q. Self-assembly of polyadeninetailed CpG oligonucleotide-gold nanoparticle nanoconjugates with immunostimulatory activity. Small, 2014, vol. 10, no. 2, pp. 368–375. DOI: 10.1002/smll.201300903

51. Zhang H., Feng S., Yan T., Zhi C., Gao X. D., Hanagata N. Polyethyleneimine-functionalized boron nitride nanospheres as efficient carriers for enhancing the immunostimulatory effect of CpG oligodeoxynucleotides. International Journal of Nanomedicine, 2015, vol. 10, pp. 5343–5353. DOI: 10.2147/IJN.S88774

52. Zheng H., Wen S., Zhang Y., Sun Z. Organosilane and polyethylene glycol functionalized magnetic mesoporous silica nanoparticles as carriers for CpG immunotherapy in vitro and in vivo. PLoS One, 2015, vol. 10, no. 10, e0140265. DOI: 10.1371/journal.pone.0140265

53. Xu Y., Claiden P., Zhu Y., Morita H., Hanagata N. Effect of amino groups of mesoporous silica nanoparticles on CpG oligodexynucleotide delivery. Science and Technology of Advanced Materials, 2015, vol. 16, no. 4, 045006. DOI: 10.1088/1468- 6996/16/4/045006

54. Tao C., Zhu Y., Li X., Hanagata N. Binding of CpG oligodeoxynucleotides to mesoporous silica nanoparticles for enhancing delivery efficiency. Microporous and Mesoporous Materials, 2015, vol. 204, pp. 91‒98. DOI: 10.1016/j.micromeso.2014.11.007

55. Mueller M., Reichardt W., Koerner J., Groettrup M. Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice. Journal of Controlled Release, 2012, vol. 162, no. 1, pp. 159–166. DOI: 10.1016/j.jconrel.2012.06.015

56. Mochizuki S., Morishita H., Kobiyama K., Aoshi T., Ishii K. J., Sakurai K. Immunization with antigenic peptides complexed with β-glucan induces potent cytotoxic T-lymphocyte activity in combination with CpG-ODNs. Journal of Controlled Release, 2015, vol. 220, pp. 495–502.

57. Miyamoto N., Mochizuki S., Fujii S., Yoshida K., Sakurai K. Adjuvant activity enhanced by cross-linked CpG-oligonucleotides in β-glucan nanogel and its antitumor effect. Bioconjugate Chemistry, 2017, vol. 28, no. 2, pp. 565‒573. DOI: 10.1021/acs.bioconjchem.6b00675

58. Schüller V. J., Heidegger S., Sandholzer N., Nickels P. C., Suhartha N. A. Endres S., Bourquin C., Liedl T. Cellular immunostimulation by CpG-sequence-coated DNA origami structures. ACS Nano, 2011, vol. 5, pp. 9696–9702.

59. Mohri K., Kusuki E., Ohtsuki S., Takahashi N., Endo M., Hidaka K., Sugiyama H., Takahashi Y., Takakura Y., Nishikawa M. Self-assembling DNA dendrimer for effective delivery of immunostimulatory CpG DNA to immune cells. Biomacromolecules, 2015, vol. 16, no. 4, pp. 1095–1101. DOI: 10.1021/bm501731f

60. Nishikawa M., Mizuno Y., Mohri K., Matsuoka N., Rattanakiat S., Takahashi Y., Funabashi H., Luo D., Takakura Y. Biodegradable CpG DNA hydrogels for sustained delivery of doxorubicin and immunostimulatory signals in tumor-bearing mice. Biomaterials, 2011, vol. 32, no. 2, pp. 488–494. DOI: 10.1016/j.biomaterials.2010.09.013

61. Mei L., Zhu G., Qiu L., Wu C., Chen H., Liang H., Cansiz S., Lv Y., Zhang X., Tan W. Self-assembled multifunctional DNA nanoflowers for the circumvention of multidrug resistance in targeted anticancer drug delivery. Nano Research, 2015, vol. 8, no. 11, pp. 3447–3460.

62. Mutwiri G. K., Nichani A. K., Babiuk S., Babiuk L. A. Strategies for enhancing the immunostimulatory effects of CpG oligodeoxynucleotides. Journal of Controlled Release, 2004, vol. 97, no. 1, pp. 1–17. DOI: 10.1016/j.jconrel.2004.02.022

63. Mutwiri G. S., van Drunen Littel-van den Hurk S., Babiuk L. A. Approaches to enhancing immune responses stimulated by CpG oligodeoxynucleotides. Advanced Drug Delivery Reviews, 2009, vol. 61, no. 3, pp. 226–232. DOI: 10.1016/j.addr.2008.12.004

64. Demoulins T., Milona P., McCullough K. C. Alginate-coated chitosan nanogels differentially modulate class-A and class-B CpG-ODN targeting of dendritic cells and intracellular delivery. Nanomedicine, 2014, vol. 10, no. 8, pp. 1739‒1749. DOI: 10.1016/j.nano.2014.06.003

65. Hanagata N. Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system. International Journal of Nanomedicine, 2012, vol. 7, pp. 2181–2195. DOI: 10.2147/IJN.S30197

66. Zhu G., Liu Y., Yang X., Kim Y. H., Zhang H., Jia R., Liao H. S., Jin A., Lin J., Aronova M., Leapman R., Nie Z., Niu G., Chen X. DNA-inorganic hybrid nanovaccine for cancer immunotherapy. Nanoscale, 2016, vol. 8, no. 12, pp. 6684–6692. DOI: 10.1039/c5nr08821f

67. Xu Z. P., Lu G. Q. Layered double hydroxide nanomaterials as potential cellular drug delivery agents. Pure and Applied Chemistry, 2006, vol. 78, no. 9, pp. 1771–1779. DOI: 10.1351/pac200678091771

68. Rives V., del Arco M., Martin C. Layered double hydroxides as drug carriers and for controlled release of non-steroidal antiinflammatory drugs (NSAIDs): a review. Journal of Controlled Release, 2013, vol. 169, pp. 28–39.

69. Olfs H. W., Torres-Dorantea L. O., Eckeltc R., Kosslickc H. Comparison of different synthesis routes for Mg–Al layered double hydroxides (LDH): Characterization of the structural phases and anion exchange properties. Applied Clay Science, 2009, vol. 43, no. 3/4, pp. 459–464.

70. Theiss F. L., Ayoko G. A., Frost R. L. Synthesis of layered double hydroxides containing Mg2+, Zn2+, Ca2+ and Al3+ layer cations by co-precipitation methods. Applied Surface Science, 2016, vol. 383, pp. 200–213. DOI: 10.1016/j.apsusc.2016.04.150

71. Aisawa S., Ohnuma Y., Hirose K., Takahashi S., Hirahara H., Narita E. Intercalation of nucleotides into layered double hydroxides by ion-exchange reaction. Applied Clay Science, 2005, vol. 28, no. 1/4, pp. 137–145.

72. Kwak S.-Y., Jeong Y.-Joo, Park J.-S., Choy J.-Ho. Bio-LDH nanohybrid for gene therapy. Solid State Ionics, 2002, vol. 151, pp. 229–234.

73. Xu Z. P., Walker T. L., Liu K., Cooper H. M., Lu G. M., Bartlett P. F. Layered double hydroxide nanoparticles as cellular delivery vectors of supercoiled plasmid DNA. International Journal of Nanomedicine, 2007, vol. 2, no. 2, pp. 163–174.

74. Kim J. Y., Choi S. J., Oh J. M., Park T., Choy J. H. Anticancer drug-inorganic nanohybrid and its cellular interaction. Journal of Nanoscience and Nanotechnology, 2007, vol. 7, no. 11, pp. 3700‒3705.

75. Manzi-Nshuti C., Chen D., Su S., Wilkie C. A. The effects of intralayer metal composition of layered double hydroxides on glass transition, dispersion, thermal and fire properties of their PMMA nanocomposites. Thermochimica Acta, 2009, vol. 495, no. 1/2, pp. 63–71.

76. Pontarollo R. A., Babiuk L. A., Hecker R., van Drunen Littel-van den Hurk S. Augmentation of cellular immune responses to bovine herpesvirus-1 glycoprotein D by vaccination with CpG-enhanced plasmid vectors. Journal of General Virology, 2002, vol. 83, pp. 2973–2981.

77. Kojima Y., Xin K. Q., Ooki T., Hamajima K., Oikawa T., Shinoda K., Ozaki T., Hoshino Y., Jounai N., Nakazawa M., Klinman D. Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine. Vaccine, 2002, vol. 20, pp. 2857–2865.

78. Juvaris BioTherapeutics announces positive data from clinical trial of JVRS-100 adjuvanted flu vaccine. Juvaris BioTherapeutics, Inc. Available at: http://www.juvaris.com/news/press/09_01_08.html (accessed 18 May 2017).

79. Bernstein D. I., Earwood J. D., Bravo F. J., Cohen G. H., Eisenberg R. J., Clark J. R., Fairman J., Cardin R. D. Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig. Vaccine, 2011, vol. 29, no. 11, pp. 2071–2078.

80. Morreya J. D., Motter N. E., Chang S., Fairman J. Breaking B and T cell tolerance using cationic lipid-DNA complexes (CLDC) as a vaccine adjuvant with hepatitis B virus (HBV) surface antigen in transgenic mice expressing HBV. Antiviral Research, 2011, vol. 90, no. 3, pp. 227–230.

81. Dong L., Liu F., Fairman J., Hong D. K., Lewis D. B., Monath T., Warner J. F., Belser J. A., Patel J., Hancock K., Katz J. M., Lu X. Cationic liposome–DNA complexes (CLDC) adjuvant enhances the immunogenicity and cross-protective efficacy of a pre-pandemic influenza A H5N1 vaccine in mice. Vaccine, 2012, vol. 30, pp. 254–264. DOI: 10.10.16/j.vaccine.2011.10.103

82. Carroll T. D., Matzinger S. R., Barry P. A., McChesney M. B., Fairman J., Miller C. J. Efficacy of influenza vaccination of elderly Rhesus Macaques is dramatically improved by addition of a cationic lipid/DNA adjuvant. Journal of Infection Diseases, 2014, vol. 209, no. 1, pp. 24–33.

83. Zinchenko A. I., Kvach S. V., Shchokolova A. S. Construction of plasmid enriched with immunostimulatory CpG motifs. Eastern European Scientific Journal, 2014, no. 3, pp. 10–13.

84. Shchekolova A. S. Elaboration of biotechnological methods of obtaining nucleic immunostimulants – CpG-DNA and cyclic di-GMP, Abstract of Ph. D. diss. Minsk, 2014. 24 p. (in Russian).

85. Hanagata N. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies. International Journal of Nanomedicine, 2017, vol. 12, pp. 515–531. DOI: 10.2147/IJN.S114477

86. Schmidt M., Hagner N., Marco A., König-Merediz S. A., Schroff M., Wittig B. Design and structural requirements of the potent and safe TLR-9 agonistic immunomodulator MGN1703. Nucleic Acid Therapeutics, 2015, vol. 25, no. 3, pp. 130–140. DOI: 10.1089/nat.2015.0533

87. Hirsh V., Paz-Ares L., Boyer M., Rosell R., Middleton G., Eberhardt W. E., Szczesna A., Reiterer P., Saleh M., Arrieta O., Bajetta E., Webb R. T., Raats J., Benner R. J., Fowst C., Meech S. J., Readett D., Schiller J. H. Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced nonsmall-cell lung cancer. Journal of Clinical Oncology, 2011, vol. 29, no. 19, pp. 2667–2674. DOI: 10.1200/JCO.2010.32.8971

88. Manegold C., van Zandwijk N., Szczesna A., Zatloukal P., Au J. S., Blasinska-Morawiec M., Serwatowski P., Krzakowski M., Jassem J., Tan E. H., Benner R. J., Ingrosso A., Meech S. J., Readett D., Thatcher N. A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-smallcell lung cancer. Annals of Oncology, 2012, vol. 23, no. 1, pp. 72–77. DOI: 10.1093/annonc/mdr030

89. Loh X. J., Ong S. J., Tung Y. T., Choo H. T. Co-delivery of drug and DNA from cationic dual-responsive micelles derived from poly(DMAEMA-co-PPGMA). Material Science and Engineering, 2013, vol. 33, no. 8, pp. 4545–4550. DOI: 10.1016/j.msec.2013.07.011

90. Makkouk A., Joshi V. B., Wongrakpanich A., Lemke C. D., Gross B. P., Salem A. K., Weiner G. J. Biodegradable microparticles loaded with doxorubicin and CpG ODN for in situ immunization against cancer. AAPS Journal, 2015, vol. 17, no. 1, pp. 184–193. DOI: 10.1208/s12248-014-9676-6

91. Mizuno Y., Naoi T., Nishikawa M., Rattanakiat S., Hamaguchi N., Hashida M., Takakura Y. Simultaneous delivery of doxorubicin and immunostimulatory CpG motif to tumors using a plasmid DNA/doxorubicin complex in mice. Journal of Controlled Release, 2010, vol. 141, no. 2, pp. 252–259. DOI: 10.1016/j.jconrel.2009.09.014

92. Brody J. D., Ai W. Z., Czerwinski D. K., Torchia J. A., Levy M., Advani R. H., Kim Y. H., Hoppe R. T., Knox S. J., Shin L. K., Wapnir I., Tibshirani R. J., Levy R. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. Journal of Clinical Oncology, 2010, vol. 28, no. 28, pp. 4324–4332. DOI: 10.1200/JCO.2010.28.9793

93. Marabelle A., Kohrt H., Caux C., Levy R. Intratumoral immunization: a new paradigm for cancer therapy. Clinical Cancer Research, 2014, vol. 20, no. 7, pp. 1747‒1756. DOI: 10.1158/1078-0432.CCR-13-2116

94. Pierce R. H., Campbell J. S., Pai S. I., Brody J. D., Kohrt H. E. In-situ tumor vaccination: bringing the fight to the tumor. Human Vaccines and Immunotherapeutics, 2015, vol. 11, no. 8, pp. 1901–1909. DOI: 10.1080/21645515.2015.1049779

95. Hu X., Wu T., Bao Y., Zhang Z. Nanotechnology based therapeutic modality to boost anti-tumor immunity and collapse tumor defense. Journal of Controlled Release, 2017, vol. 256, pp. 26‒45. DOI: 10.1016/j.jconrel.2017.04.026


Review

Views: 685


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1029-8940 (Print)
ISSN 2524-230X (Online)