Distinct immunological activation profiles of dSLIM ® and promune ® depend on their different structural context

Immunity, Inflammation and Disease

Volumn 4, Issue 4, 2016, Pages 446-462

  Kapp, Kerstin ^a   Schneider, Jacqueline ^a   Schneider, Lisa ^a   Gollinge, Nadine ^a   Jänsch, Stefanie ^a   Schroff, Matthias ^a   Wittig, Burghardt ^b   Kleuss, Christiane ^a  

^a MOLOGEN AG   (Germany)

^b FREIE UNIVERSITÄT BERLIN   (Germany)

Author keywords

Cancer immunotherapy; Plasmacytoid dendritic cells; Structure function relationship

Indexed keywords

EID: 85029102600     PISSN: None     EISSN: 20504527     Source Type: Journal    
DOI: 10.1002/iid3.126     Document Type: Article

References (57)

1. Chen, D. S., and I. Mellman. 2013. Oncology meets immunology: the cancer-immunity cycle. Immunity 39:1–10.
2. Iwasaki, A., and R. Medzhitov. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5:987–995.
3. Kawai, T., and S. Akira. 2010. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11:373–384.
4. Zelenay, S., and E. S. C. Reis. 2013. Adaptive immunity after cell death. Trends Immunol. 34:329–335.
5. Klinman, D. M., G. Yamshchikov, and Y. Ishigatsubo. 1997. Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158:3635–3639.
6. Krieg, A. M., A. K. Yi, S. Matson, T. J. Waldschmidt, G. A. Bishop, R. Teasdale, G. A. Koretzky, and D. M. Klinman. 1995. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374:546–549.
7. Roman, M., E. Martin-Orozco, J. S. Goodman, M. D. Nguyen, Y. Sato, A. Ronaghy, R. S. Kornbluth, D. D. Richman, D. A. Carson, and E. Raz. 1997. Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat. Med. 3:849–854.
8. Yamamoto, S., T. Yamamoto, T. Kataoka, E. Kuramoto, O. Yano, and T. Tokunaga. 1992. Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN [correction of INF] and augment IFN-mediated [correction of INF] natural killer activity. J. Immunol. 148:4072–4076.
9. Oka, T., S. Hikoso, O. Yamaguchi, M. Taneike, T. Takeda, T. Tamai, J. Oyabu, T. Murakawa, H. Nakayama, K. Nishida, S. Akira, A. Yamamoto, I. Komuro, and K. Otsu. 2012. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 485:251–255.
10. Hemmi, H., O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, K. Hoshino, H. Wagner, K. Takeda, and S. Akira. 2000. A toll-like receptor recognizes bacterial DNA. Nature 408:740–745.
11. Elias, F., J. Flo, R. A. Lopez, J. Zorzopulos, A. Montaner, and J. M. Rodriguez. 2003. Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs. J. Immunol. 171:3697–3704.
12. Ahmad-Nejad, P., H. Hacker, M. Rutz, S. Bauer, R. M. Vabulas, and H. Wagner. 2002. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur. J. Immunol. 32:1958–1968.
13. Zhang, Q., M. Raoof, Y. Chen, Y. Sumi, T. Sursal, W. Junger, K. Brohi, K. Itagaki, and C. J. Hauser. 2010. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–107.
14. Hornung, V., S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdörfer, T. Giese, S. Endres, and G. Hartmann. 2002. Quantitative expression of toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168:4531–4537.
15. Guiducci, C., R. L. Coffman, and F. J. Barrat. 2009. Signalling pathways leading to IFN-alpha production in human plasmacytoid dendritic cell and the possible use of agonists or antagonists of TLR7 and TLR9 in clinical indications. J. Intern. Med. 265:43–57.
16. Kawai, T., and S. Akira. 2007. TLR signaling. Semin. Immunol. 19:24–32.
17. Colonna, M., G. Trinchieri, and Y. J. Liu. 2004. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5:1219–1226.
18. Stein, C. A., and Y. C. Cheng. 1993. Antisense oligonucleotides as therapeutic agents-is the bullet really magical? Science 261:1004–1012.
19. Krug, A., S. Rothenfusser, V. Hornung, B. Jahrsdörfer, S. Blackwell, Z. K. Ballas, S. Endres, A. M. Krieg, and G. Hartmann. 2001. Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells. Eur. J. Immunol. 31:2154–2163.
20. Verthelyi, D., K. J. Ishii, M. Gursel, F. Takeshita, and D. M. Klinman. 2001. Human peripheral blood cells differentially recognize and respond to two distinct CPG motifs. J. Immunol. 166:2372–2377.
21. Hartmann, G., and A. M. Krieg. 2000. Mechanism and function of a newly identified CpG DNA motif in human primary B cells. J. Immunol. 164:944–953.
22. Marshall, J. D. 2003. Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions. J. Leukoc. Biol. 73:781–792.
23. Hartmann, G., J. Battiany, H. Poeck, M. Wagner, M. Kerkmann, N. Lubenow, S. Rothenfusser, and S. Endres. 2003. Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells. Eur. J. Immunol. 33:1633–1641.
24. Samulowitz, U., M. Weber, R. Weeratna, E. Uhlmann, B. Noll, A. M. Krieg, and J. Vollmer. 2010. A novel class of immune-stimulatory CpG oligodeoxynucleotides unifies high potency in type I interferon induction with preferred structural properties. Oligonucleotides 20:93–101.
25. Kapp, K., C. Kleuss, M. Schroff, and B. Wittig. 2014. Genuine immunomodulation with dSLIM. Mol Ther Nucleic Acids 3: e170.
26. Schmoll, H. J., B. Wittig, D. Arnold, J. Riera-Knorrenschild, D. Nitsche, H. Kroening, F. Mayer, J. Andel, R. Ziebermayr, and W. Scheithauer. 2014. Maintenance treatment with the immunomodulator MGN1703, a Toll-like receptor 9 (TLR9) agonist, in patients with metastatic colorectal carcinoma and disease control after chemotherapy: a randomised, doubleblind, placebo-controlled trial. J. Cancer Res. Clin. Oncol. 140:1615–1624.
27. Hartmann, G., R. D. Weeratna, Z. K. Ballas, P. Payette, S. Blackwell, I. Suparto, W. L. Rasmussen, M. Waldschmidt, D. Sajuthi, R. H. Purcell, H. L. Davis, and A. M. Krieg. 2000. Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. J. Immunol. 164:1617–1624.
28. Hirsh, V., L. Paz-Ares, M. Boyer, R. Rosell, G. Middleton, W. E. Eberhardt, A. Szczesna, P. Reiterer, M. Saleh, O. Arrieta, E. Bajetta, R. T. Webb, J. Raats, R. J. Benner, C. Fowst, S. J. Meech, D. Readett, and J. H. Schiller. 2011. Randomized phase III trial of paclitaxel/carboplatin with or without PF- 3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer. J. Clin. Oncol. 29:2667–2674.
29. Behrens, E. M., S. W. Canna, K. Slade, S. Rao, P. A. Kreiger, M. Paessler, T. Kambayashi, and G. A. Koretzky. 2011. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J. Clin. Invest. 121:2264–2277.
30. Heikenwalder, M., M. Polymenidou, T. Junt, C. Sigurdson, H. Wagner, S. Akira, R. Zinkernagel, and A. Aguzzi. 2004. Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat. Med. 10:187–192.
31. Henry, S. P., G. Beattie, G. Yeh, A. Chappel, P. Giclas, A. Mortari, M. A. Jagels, D. J. Kornbrust, and A. A. Levin. 2002. Complement activation is responsible for acute toxicities in rhesus monkeys treated with a phosphorothioate oligodeoxynucleotide. Int. Immunopharmacol. 2:1657–1666.
32. Henry, S. P., W. Novotny, J. Leeds, C. Auletta, and D. J. Kornbrust. 1997. Inhibition of coagulation by a phosphorothioate oligonucleotide. Antisense Nucleic Acid Drug Dev. 7:503–510.
33. Sheehan, J. P., and H. C. Lan. 1998. Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex. Blood 92:1617–1625.
34. Biesen, R., C. Demir, F. Barkhudarova, J. R. Grün, M. Steinbrich-Zöllner, M. Backhaus, T. Häupl, M. Rudwaleit, G. Riemekasten, A. Radbruch, F. Hiepe, G. R. Burmester, and A. Grützkau. 2008. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 58:1136–1145.
35. York, M. R., T. Nagai, A. J. Mangini, R. Lemaire, J. M. van Seventer, and R. Lafyatis. 2007. A macrophage marker, Siglec- 1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and tolllike receptor agonists. Arthritis Rheum. 56:1010–1020.
36. Symons, J. A., A. Alcami, and G. L. Smith. 1995. Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity. Cell 81:551–560.
37. Blackwell, S. E., and A. M. Krieg. 2003. CpG-A-induced monocyte IFN-gamma-inducible protein-10 production is regulated by plasmacytoid dendritic cell-derived IFN-alpha. J. Immunol. 170:4061–4068.
38. Schmidt, M., K. Kapp, D. Oswald, M. Schroff, B. Wittig, and A. Zurlo. 2015. The immunotherapeutic TLR-9 agonist MGN1703–Pharmacokinetic and pharmacodynamic data from healthy volunteers and cancer patients. 2nd Immunotherapy of Cancer Conference. Munich, Germany. Eur. J. Cancer S12.
39. Millward, M., C. Underhill, S. Lobb, J. McBurnie, S. J. Meech, J. Gomez-Navarro, M. A. Marshall, B. Huang, and C. B. Mather. 2013. Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours. Br. J. Cancer 108:1998–2004.
40. Gonzalez-Navajas, J. M., J. Lee, M. David, and E. Raz. 2012. Immunomodulatory functions of type I interferons. Nat. Rev. Immunol. 12:125–135.
41. Arenberg, D. A., S. L. Kunkel, P. J. Polverini, S. B. Morris, M. D. Burdick, M. C. Glass, D. T. Taub, M. D. Iannettoni, R. I. Whyte, and R. M. Strieter. 1996. Interferongamma- inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J. Exp. Med. 184:981–992.
42. Boehm, U., T. Klamp, M. Groot, and J. C. Howard. 1997. Cellular responses to interferon-gamma. Annu. Rev. Immunol. 15:749–795.
43. Asano, K., A. Nabeyama, Y. Miyake, C. H. Qiu, A. Kurita, M. Tomura, O. Kanagawa, S. Fujii, and M. Tanaka. 2011. CD169- positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 34:85–95.
44. Randolph, G. J., C. Jakubzick, and C. Qu. 2008. Antigen presentation by monocytes and monocyte-derived cells. Curr. Opin. Immunol. 20:52–60.
45. Vivier, E., S. Ugolini, D. Blaise, C. Chabannon, and L. Brossay. 2012. Targeting natural killer cells and natural killer T cells in cancer. Nat. Rev. Immunol. 12:239–252.
46. Diamond, M. S., M. Kinder, H. Matsushita, M. Mashayekhi, G. P. Dunn, J. M. Archambault, H. Lee, C. D. Arthur, J. M. White, U. Kalinke, K. M. Murphy, and R. D. Schreiber. 2011. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J. Exp. Med. 208: 1989–2003.
47. + dendritic cells. J. Exp. Med. 208:2005–2016.
48. Poeck, H., M. Wagner, J. Battiany, S. Rothenfusser, D. Wellisch, V. Hornung, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann. 2004. Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood 103:3058–3064.
49. Krieg, A. M. 2006. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Discov. 5:471–484.
50. Koch, A. E., P. J. Polverini, S. L. Kunkel, L. A. Harlow, L. A. DiPietro, V. M. Elner, S. G. Elner, and R. M. Strieter. 1992. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801.
51. Benlahrech, A., H. Donaghy, G. Rozis, M. Goodier, L. Klavinskis, F. Gotch, and S. Patterson. 2009. Human NK cell up-regulation of CD69, HLA-DR, interferon gamma secretion and cytotoxic activity by plasmacytoid dendritic cells is regulated through overlapping but different pathways. Sensors 9:386–403.
52. Romagnani, C., M. Della Chiesa, S. Kohler, B. Moewes, A. Radbruch, L. Moretta, A. Moretta, and A. Thiel. 2005. Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells. Eur. J. Immunol. 35:2452–2458.
53. Vollmer, J., A. Janosch, M. Laucht, Z. K. Ballas, C. Schetter, and A. M. Krieg. 2002. Highly immunostimulatory CpG-free oligodeoxynucleotides for activation of human leukocytes. Antisense Nucleic Acid Drug Dev. 12:165–175.
54. Vollmer, J., R. D. Weeratna, M. Jurk, U. Samulowitz, M. J. McCluskie, P. Payette, H. L. Davis, C. Schetter, and A. M. Krieg. 2004. Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation. Immunology 113:212–223.
55. Chinnathambi, S., S. Chen, S. Ganesan, and N. Hanagata. 2012. Binding mode of CpG oligodeoxynucleotides to nanoparticles regulates bifurcated cytokine induction via Toll-like receptor 9. Sci. Rep. 2:534.
56. Gungor, B., F. C. Yagci, G. Tincer, B. Bayyurt, E. Alpdundar, S. Yildiz, M. Ozcan, I. Gursel, and M. Gursel. 2014. CpGODN nanorings induce IFNalpha from plasmacytoid dendritic cells and demonstrate potent vaccine adjuvant activity. Sci. Transl. Med. 6:235ra61.
57. Ballas, Z. K., W. L. Rasmussen, and A. M. Krieg. 1996. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol. 157:1840–1845.