A tumor-peptide based nanoparticle vaccine elicits efficient tumor … · 2019. 4. 6. · 1 A tumor-peptide based nanoparticle vaccine elicits efficient tumor growth control in anti-tumor
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
A tumor-peptide based nanoparticle vaccine elicits efficient tumor
growth control in anti-tumor immunotherapy
Carolin Heße1, Sebastian Kollenda2, Olga Rotan2, Eva Pastille1, Alexandra
Adamczyk1, Christina Wenzek1, Wiebke Hansen1, Matthias Epple2, Jan Buer1, Astrid
M. Westendorf1, Torben Knuschke1*
1Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen,
Essen, Germany
2Institute of Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE),
Essen, Germany
Running title: Peptide nanoparticle vaccine for anti-tumor immunotherapy
Keywords: nanoparticles; therapeutic vaccine; tumor; T cell immunity; type I interferons;
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
nanoparticles efficiently facilitated to overcome immune tolerance which is often seen
in patients with solid organ malignancies (49-51).
In conclusion, we here demonstrate that CpG and antigen functionalized CaP
nanoparticles have a high potential for therapeutic vaccination against tumor disease.
Delivery of these molecules by CaP nanoparticles is more efficient than conventional
application of soluble CpG/antigen to repress tumor growth. This effect strongly
correlates with the reinforcement of cytotoxic CD8+ T cell immunity. A combination
therapy including PD-L1 blockade leads to a high effective tumor growth control.
Furthermore, we present a translational approach for the application of CaP
nanoparticles as a potent cancer vaccine vehicle by encapsulating a primary tumor
cell derived lysate.
Acknowledgements
T. Knuschke, A.M. Westendorf, J. Buer and W. Hansen were supported by the
Deutsche Forschungsgemeinschaft (DFG)-funded research training group RTG
1949.
We thank Svenja Groten, Christina Liebig, Christian Fehring and Mechthild Hemmler-
Rohloff for excellent technical assistance.
References
1. Vyas JM, Van der Veen AG, Ploegh HL. The known unknowns of antigen processing and presentation. Nat Rev Immunol 2008;8:607-18
2. Bobisse S, Foukas PG, Coukos G, Harari A. Neoantigen-based cancer immunotherapy. Ann Transl Med 2016;4:262
3. Kumai T, Kobayashi H, Harabuchi Y, Celis E. Peptide vaccines in cancer-old concept revisited. Curr Opin Immunol 2017;45:1-7
4. Purcell AW, McCluskey J, Rossjohn J. More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 2007;6:404-14
5. Emens LA, Butterfield LH, Hodi FS, Jr., Marincola FM, Kaufman HL. Cancer immunotherapy trials: leading a paradigm shift in drug development. J Immunother Cancer 2016;4:42
6. Antonilli M, Rahimi H, Visconti V, Napoletano C, Ruscito I, Zizzari IG, et al. Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial. Int J Oncol 2016;48:1369-78
7. Mittendorf EA, Ardavanis A, Litton JK, Shumway NM, Hale DF, Murray JL, et al. Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence. Oncotarget 2016;7:66192-201
8. Disis ML, Gad E, Herendeen DR, Lai VP, Park KH, Cecil DL, et al. A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. Cancer Prev Res (Phila) 2013;6:1273-82
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
9. de Titta A, Ballester M, Julier Z, Nembrini C, Jeanbart L, van der Vlies AJ, et al. Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose. Proc Natl Acad Sci U S A 2013;110:19902-7
10. Scheiermann J, Klinman DM. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer. Vaccine 2014;32:6377-89
11. Sokolova V, Knuschke T, Kovtun A, Buer J, Epple M, Westendorf AM. The use of calcium phosphate nanoparticles encapsulating Toll-like receptor ligands and the antigen hemagglutinin to induce dendritic cell maturation and T cell activation. Biomaterials 2010;31:5627-33
12. Epple M, Ganesan K, Heumann R, Klesing J, Kovtun A, Neumann S, et al. Application of calcium phosphate nanoparticles in biomedicine. Journal of Materials Chemistry 2010;20:18-23
13. Maitra A. Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy. Expert Rev Mol Diagn 2005;5:893-905
14. Sokolova V, Rotan O, Klesing J, Nalbant P, Buer J, Knuschke T, et al. Calcium phosphate nanoparticles as versatile carrier for small and large molecules across cell membranes. Journal of Nanoparticle Research 2012;14:910
15. Neumann S, Kovtun A, Dietzel ID, Epple M, Heumann R. The use of size-defined DNA-functionalized calcium phosphate nanoparticles to minimise intracellular calcium disturbance during transfection. Biomaterials 2009;30:6794-802
16. Sokolova V, Kozlova D, Knuschke T, Buer J, Westendorf AM, Epple M. Mechanism of the uptake of cationic and anionic calcium phosphate nanoparticles by cells. Acta Biomater 2013;9:7527-35
17. Knuschke T, Sokolova V, Rotan O, Wadwa M, Tenbusch M, Hansen W, et al. Immunization with biodegradable nanoparticles efficiently induces cellular immunity and protects against influenza virus infection. J Immunol 2013;190:6221-9
18. Knuschke T, Bayer W, Rotan O, Sokolova V, Wadwa M, Kirschning CJ, et al. Prophylactic and therapeutic vaccination with a nanoparticle-based peptide vaccine induces efficient protective immunity during acute and chronic retroviral infection. Nanomedicine 2014;10:1787-98
19. Knuschke T, Rotan O, Bayer W, Sokolova V, Hansen W, Sparwasser T, et al. Combination of nanoparticle-based therapeutic vaccination and transient ablation of regulatory T cells enhances anti-viral immunity during chronic retroviral infection. Retrovirology 2016;13:24
20. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science 2018;359:1350-5
21. Morgan DJ, Liblau R, Scott B, Fleck S, McDevitt HO, Sarvetnick N, et al. CD8(+) T cell-mediated spontaneous diabetes in neonatal mice. J Immunol 1996;157:978-83
22. Sokolova V, Knuschke T, Buer J, Westendorf AM, Epple M. Quantitative determination of the composition of multi-shell calcium phosphate-oligonucleotide nanoparticles and their application for the activation of dendritic cells. Acta Biomater 2011;7:4029-36
23. Pearce EL, Mullen AC, Martins GA, Krawczyk CM, Hutchins AS, Zediak VP, et al. Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 2003;302:1041-3
24. Knuschke T, Rotan O, Bayer W, Kollenda S, Dickow J, Sutter K, et al. Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8+ T Cell Responses During Chronic Retroviral Infection. Frontiers in Immunology 2018;9:614
25. Goldszmid RS, Idoyaga J, Bravo AI, Steinman R, Mordoh J, Wainstok R. Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma. J Immunol 2003;171:5940-7
26. Melero I, Vile RG, Colombo MP. Feeding dendritic cells with tumor antigens: self-service buffet or a la carte? Gene Ther 2000;7:1167-70
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
27. Rainone V, Martelli C, Ottobrini L, Biasin M, Texido G, Degrassi A, et al. Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy. PLoS One 2016;11:e0146622
28. Baines J, Celis E. Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. Clin Cancer Res 2003;9:2693-700
29. 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
30. Ohno S, Okuyama R, Aruga A, Sugiyama H, Yamamoto M. Phase I trial of Wilms' Tumor 1 (WT1) peptide vaccine with GM-CSF or CpG in patients with solid malignancy. Anticancer Res 2012;32:2263-9
31. Madan RA, Bilusic M, Heery C, Schlom J, Gulley JL. Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin Oncol 2012;39:296-304
32. Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 2016;534:396-401
33. Soysal SD, Tzankov A, Muenst SE. Role of the Tumor Microenvironment in Breast Cancer. Pathobiology 2015;82:142-52
34. Dellacherie MO, Li AW, Lu BY, Mooney DJ. Covalent Conjugation of Peptide Antigen to Mesoporous Silica Rods to Enhance Cellular Responses. Bioconjug Chem 2018;29:733-741
35. Suzuki Y, Wakita D, Chamoto K, Narita Y, Tsuji T, Takeshima T, et al. Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity. Cancer Res 2004;64:8754-60
36. Wakita D, Chamoto K, Zhang Y, Narita Y, Noguchi D, Ohnishi H, et al. An indispensable role of type-1 IFNs for inducing CTL-mediated complete eradication of established tumor tissue by CpG-liposome co-encapsulated with model tumor antigen. Int Immunol 2006;18:425-34
37. Muraoka D, Kato T, Wang L, Maeda Y, Noguchi T, Harada N, et al. Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells. J Immunol 2010;185:3768-76
38. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM. CpG DNA as a vaccine adjuvant. Expert Rev Vaccines 2011;10:499-511
39. Barton GM, Medzhitov R. Control of adaptive immune responses by Toll-like receptors. Curr Opin Immunol 2002;14:380-3
40. Ugurel S, Schrama D, Keller G, Schadendorf D, Brocker EB, Houben R, et al. Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother 2008;57:685-91
41. Rapp M, Grassmann S, Chaloupka M, Layritz P, Kruger S, Ormanns S, et al. C-C chemokine receptor type-4 transduction of T cells enhances interaction with dendritic cells, tumor infiltration and therapeutic efficacy of adoptive T cell transfer. Oncoimmunology 2016;5:e1105428
42. Pylaeva E, Lang S, Jablonska J. The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils. Front Immunol 2016;7:629
43. Muller L, Aigner P, Stoiber D. Type I Interferons and Natural Killer Cell Regulation in Cancer. Front Immunol 2017;8:304
44. Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, et al. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 2003;424:516-23
45. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 2013;14:1014-22
46. Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015;373:1270-1
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
49. Bhardwaj N. Harnessing the immune system to treat cancer. J Clin Invest 2007;117:1130-6 50. Nestle FO, Farkas A, Conrad C. Dendritic-cell-based therapeutic vaccination against cancer.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764
Published OnlineFirst April 8, 2019.Mol Cancer Ther Carolin Heße, Sebastian Kollenda, Olga Rotan, et al. tumor growth control in anti-tumor immunotherapyA tumor-peptide based nanoparticle vaccine elicits efficient
Updated version
10.1158/1535-7163.MCT-18-0764doi:
Access the most recent version of this article at:
Manuscript
Authorbeen edited. Author manuscripts have been peer reviewed and accepted for publication but have not yet
E-mail alerts related to this article or journal.Sign up to receive free email-alerts
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 8, 2019; DOI: 10.1158/1535-7163.MCT-18-0764