A novel RNA-based adjuvant combines strong immunostimulatory capacities with a favorable safety profile

International Journal of Cancer

Volumn 137, Issue 2, 2015, Pages 372-384

  Heidenreich, Regina ^a   Jasny, Edith ^a   Kowalczyk, Aleksandra ^a   Lutz, Johannes ^a   Probst, Jochen ^b   Baumhof, Patrick ^a   Scheel, Birgit ^a   Voss, Söhnke ^a   Kallen, Karl Josef ^a   Fotin Mleczek, Mariola ^a  

^a CureVac GmbH   (Germany)

^b IDT Biologika GmbH   (Germany)

Author keywords

adjuvant; cancer immunotherapy; HPV 16; peptide vaccine; poly(I:C); protein vaccine; RNA; RNAdjuvant; TC 1; TLR

Indexed keywords

IMMUNOLOGICAL ADJUVANT; PROTEIN E7; RNA VACCINE; RNADJUVANT; UNCLASSIFIED DRUG; CANCER VACCINE; CYTOKINE; LONG UNTRANSLATED RNA; ONCOGENE PROTEIN E7, HUMAN PAPILLOMAVIRUS TYPE 16; PEPTIDE; POLYINOSINIC POLYCYTIDYLIC ACID;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER IMMUNIZATION; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE RELEASE; FEMALE; HUMAN; HUMAN CELL; HUMAN PAPILLOMAVIRUS TYPE 16; HUMORAL IMMUNITY; IMMUNOSTIMULATION; LYMPH NODE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR GROWTH; TUMOR REGRESSION; UPREGULATION; UTERINE CERVIX CANCER; ANIMAL; BAGG ALBINO MOUSE; C57BL MOUSE; DISEASE MODEL; FLOW CYTOMETRY; GENETICS; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; METABOLISM; TRANSFORMED CELL LINE; TREATMENT OUTCOME; UTERINE CERVICAL NEOPLASMS;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; CANCER VACCINES; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TRANSFORMED; CYTOKINES; DISEASE MODELS, ANIMAL; FEMALE; FLOW CYTOMETRY; HUMANS; IMMUNOLOGIC MEMORY; MICE, INBRED BALB C; MICE, INBRED C57BL; PAPILLOMAVIRUS E7 PROTEINS; PEPTIDES; POLY I-C; RNA, LONG NONCODING; TREATMENT OUTCOME; UTERINE CERVICAL NEOPLASMS;

EID: 84929288176     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.29402     Document Type: Article

References (54)

1. Brewer JM, Conacher M, Satoskar A, et al. In interleukin-4-deficient mice, alum not only generates T helper 1 responses equivalent to Freund's complete adjuvant, but continues to induce T helper 2 cytokine production. Eur J Immunol 1996; 26: 2062-6.
2. Schirmbeck R, Melber K, Mertens T, et al. Antibody and cytotoxic T-cell responses to soluble hepatitis B virus (HBV) S antigen in mice: implication for the pathogenesis of HBV-induced hepatitis. J Virol 1994; 68: 1418-25.
3. Traquina P, Morandi M, Contorni M, et al. MF59 adjuvant enhances the antibody response to recombinant hepatitis B surface antigen vaccine in primates. J Infect Dis 1996; 174: 1168-75.
4. Guy B,. The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol 2007; 5: 505-17.
5. Galluzzi L, Vacchelli E, Eggermont A, et al. Trial watch: experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012; 1: 699-716.
6. Vacchelli E, Galluzzi L, Eggermont A, et al. Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012; 1: 894-907.
7. Miconnet I, Koenig S, Speiser D, et al. CpG are efficient adjuvants for specific CTL induction against tumor antigen-derived peptide. J Immunol Baltim Md 1950 2002; 168: 1212-8.
8. Davila E, Kennedy R, Celis E,. Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide vaccination, CpG-oligodeoxynucleotide adjuvant, and CTLA-4 blockade. Cancer Res 2003; 63: 3281-8.
9. Perret R, Sierro SR, Botelho NK, et al. Adjuvants that improve the ratio of antigen-specific effector to regulatory T cells enhance tumor immunity. Cancer Res 2013; 73: 6597-608.
10. Machiels J-P, Kaminsky M-C, Keller U, et al. Phase ib trial of the Toll-like receptor 9 agonist IMO-2055 in combination with 5-fluorouracil, cisplatin, and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck. Invest New Drugs 2013; 31: 1207-16.
11. Kuball J, de Boer K, Wagner E, et al. Pitfalls of vaccinations with WT1-, proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909. Cancer Immunol Immunother CII 2011; 60: 161-71.
12. Belani CP, Nemunaitis JJ, Chachoua A, et al. Phase 2 trial of erlotinib with or without PF-3512676 (CPG 7909, a Toll-like receptor 9 agonist) in patients with advanced recurrent EGFR-positive non-small cell lung cancer. Cancer Biol Ther 2013; 14: 557-63.
13. Gungor B, Yagci FC, Tincer G, et al. CpG ODN nanorings induce IFNα from plasmacytoid dendritic cells and demonstrate potent vaccine adjuvant activity. Sci Transl Med 2014; 6: 235ra61.
14. Salem ML, El-Naggar SA, Kadima A, et al. The adjuvant effects of the toll-like receptor 3 ligand polyinosinic-cytidylic acid poly (I:C) on antigen-specific CD8+ T cell responses are partially dependent on NK cells with the induction of a beneficial cytokine milieu. Vaccine 2006; 24: 5119-32.
15. Forte G, Rega A, Morello S, et al. Polyinosinic-polycytidylic acid limits tumor outgrowth in a mouse model of metastatic lung cancer. J Immunol Baltim Md 1950 2012; 188: 5357-64.
16. Cui Z, Qiu F,. Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model. Cancer Immunol Immunother CII 2006; 55: 1267-79.
17. Ichinohe T, Ainai A, Ami Y, et al. Intranasal administration of adjuvant-combined vaccine protects monkeys from challenge with the highly pathogenic influenza a H5N1 virus. J Med Virol 2010; 82: 1754-61.
18. Caskey M, Lefebvre F, Filali-Mouhim A, et al. Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med 2011; 208: 2357-66.
19. Scheel B, Braedel S, Probst J, et al. Immunostimulating capacities of stabilized RNA molecules. Eur J Immunol 2004; 34: 537-47.
20. Diebold SS, Kaisho T, Hemmi H, et al. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004; 303: 1529-31.
21. Heil F, Hemmi H, Hochrein H, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004; 303: 1526-9.
22. Fotin-Mleczek M, Duchardt KM, Lorenz C, et al. Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity J Immunother Hagerstown Md 1997 2011; 34: 1-15.
23. Lin KY, Guarnieri FG, Staveley-O'Carroll KF, et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 1996; 56: 21-6.
24. Zwaveling S, Ferreira Mota SC, Nouta J, et al. Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides J Immunol Baltim Md 1950 2002; 169: 350-8.
25. Lin C-T, Hung C-F, Juang J, et al. Boosting with recombinant vaccinia increases HPV-16 E7-specific T cell precursor frequencies and antitumor effects of HPV-16 E7-expressing sindbis virus replicon particles. Mol Ther 2003; 8: 559-66.
26. De Bruijn ML, Schuurhuis DH, Vierboom MP, et al. Immunization with human papillomavirus type 16 (HPV16) oncoprotein-loaded dendritic cells as well as protein in adjuvant induces MHC class I-restricted protection to HPV16-induced tumor cells. Cancer Res 1998; 58: 724-31.
27. Peng S, Ji H, Trimble C, et al. Development of a DNA vaccine targeting human papillomavirus type 16 oncoprotein E6. J Virol 2004; 78: 8468-76.
28. Irmler M, Hertig S, MacDonald HR, et al. Granzyme a is an interleukin 1 beta-converting enzyme. J Exp Med 1995; 181: 1917-22.
29. Guma M, Ronacher L, Liu-Bryan R, et al. Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum 2009; 60: 3642-50.
30. Joosten LAB, Netea MG, Fantuzzi G, et al. Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum 2009; 60: 3651-62.
31. Marrack P, McKee AS, Munks MW,. Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol 2009; 9: 287-93.
32. Lindblad EB,. Aluminium compounds for use in vaccines. Immunol Cell Biol 2004; 82: 497-505.
33. Huber JP, Farrar JD,. Regulation of effector and memory T-cell functions by type I interferon. Immunology 2011; 132: 466-74.
34. Hervas-Stubbs S, Riezu-Boj J-I, Gonzalez I, et al. Effects of IFN-α as a signal-3 cytokine on human naïve and antigen-experienced CD8(+) T cells. Eur J Immunol 2010; 40: 3389-402.
35. Gujer C, Sandgren KJ, Douagi I, et al. IFN-α produced by human plasmacytoid dendritic cells enhances T cell-dependent naïve B cell differentiation. J Leukoc Biol 2011; 89: 811-21.
36. Guarda G, So A,. Regulation of inflammasome activity. Immunology 2010; 130: 329-36.
37. Wesa AK, Galy A,. IL-1 beta induces dendritic cells to produce IL-12. Int Immunol 2001; 13: 1053-61.
38. Mosca F, Tritto E, Muzzi A, et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA 2008; 105: 10501-6.
39. Li H, Nookala S, Re F,. Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1beta and IL-18 release. J Immunol Baltim Md 1950 2007; 178: 5271-6.
40. García MA, Gil J, Ventoso I, et al. Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. Microbiol Mol Biol Rev 2006; 70: 1032-60.
41. Onomoto K, Jogi M, Yoo J-S, et al. Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity. PloS One 2012; 7: e43031
42. Querec TD, Akondy RS, Lee EK, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 2009; 10: 116-25.
43. Caproni E, Tritto E, Cortese M, et al. MF59 and Pam3CSK4 boost adaptive responses to influenza subunit vaccine through an IFN type I-independent mechanism of action. J Immunol Baltim Md 1950 2012; 188: 3088-98.
44. Welters MJP, Kenter GG, Piersma SJ, et al. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin Cancer Res Off J Am Assoc Cancer Res 2008; 14: 178-87.
45. Van Poelgeest MIE, Welters MJP, van Esch EMG, et al. HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial. J Transl Med 2013; 11: 88.
46. Zent CS, Smith BJ, Ballas ZK, et al. Phase I clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia. Leuk Lymph 2012; 53: 211-7.
47. Link BK, Ballas ZK, Weisdorf D, et al. Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-hodgkin lymphoma. J Immunother Hagerstown Md 1997 2006; 29: 558-68.
48. Mutwiri G, Gerdts V, van Drunen Littel-van den Hurk S, et al. Combination adjuvants: the next generation of adjuvants? Expert Rev Vaccines 2011; 10: 95-107.
49. Kasturi SP, Skountzou I, Albrecht RA, et al. Programming the magnitude and persistence of antibody responses with innate immunity. Nature 2011; 470: 543-7.
50. Perrot I, Deauvieau F, Massacrier C, et al. TLR3 and Rig-like receptor on myeloid dendritic cells and Rig-like receptor on human NK cells are both mandatory for production of IFN-gamma in response to double-stranded RNA. J Immunol Baltim Md 1950 2010; 185: 2080-8.
51. Park J-S, Kim H-S, Park H-M, et al. Efficient induction of anti-tumor immunity by a TAT-CEA fusion protein vaccine with poly(I:C) in a murine colorectal tumor model. Vaccine 2011; 29: 8642-8.
52. Chin AI, Miyahira AK, Covarrubias A, et al. Toll-like receptor 3-mediated suppression of TRAMP prostate cancer shows the critical role of type I interferons in tumor immune surveillance. Cancer Res 2010; 70: 2595-603.
53. Llopiz D, Dotor J, Zabaleta A, et al. Combined immunization with adjuvant molecules poly(I:C) and anti-CD40 plus a tumor antigen has potent prophylactic and therapeutic antitumor effects. Cancer Immunol Immunother CII 2008; 57: 19-29.
54. Salem ML, Kadima AN, Cole DJ, et al. Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity. J Immunother Hagerstown Md 1997 2005; 28: 220-8.