A facile approach to enhance antigen response for personalized cancer vaccination
Source abstract
Abstract
Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhance antigen immunogenicity. The MSR-PEI vaccine significantly enhanced host dendritic cell activation and T-cell response over the existing MSR vaccine and bolus vaccine formulations. Impressively, a single injection of the MSR-PEI vaccine using an E7 peptide completely eradicated large, established TC-1 tumours in about 80% of mice and generated immunological memory. When immunized with a pool of B16F10 or CT26 neoantigens, the MSR-PEI vaccine eradicated established lung metastases, controlled tumour growth and synergized with anti-CTLA4 therapy. Our findings from three independent tumour models suggest that the MSR-PEI vaccine approach may serve as a facile and powerful multi-antigen platform to enable robust personalized cancer vaccination.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Immunotherapy and Immune Responses · Cancer Immunotherapy and Biomarkers · vaccines and immunoinformatics approaches
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (35)
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1. Gubin, M. M., Artyomov, M. N., Mardis, E. R. & Schreiber, R. D. Tumor neoantigens: building a framework for personalized cancer immunotherapy. J. Clin. Invest. 125, 3413–3421 (2015).10.1172/JCI80008 ↗
2. Schumacher, T. N. & Schreiber, R. D. Neoantigens in cancer immunotherapy. Science 348, 69–74 (2015).10.1126/science.aaa4971 ↗
3. Hacohen, N., Fritsch, E. F., Carter, T. A., Lander, E. S. & Wu, C. J. Getting personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunol. Res. 1, 11–15 (2013).10.1158/2326-6066.CIR-13-0022 ↗
4. Linnemann, C. et al. High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nat. Med. 21, 81–85 (2015).10.1038/nm.3773 ↗
5. Kreiter, S. et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520, 692–696 (2015).10.1038/nature14426 ↗
6. Ott, P. A. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547, 217–221 (2017).10.1038/nature22991 ↗
7. van der Burg, S. H., Arens, R., Ossendorp, F., van Hall, T. & Melief, C. J. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat. Rev. Cancer 16, 219–233 (2016).10.1038/nrc.2016.16 ↗
8. Moon, J. J. et al. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat. Mater. 10, 243–251 (2011).10.1038/nmat2960 ↗
9. Liu, H. et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507, 519–522 (2014).10.1038/nature12978 ↗
10. Cho, N. H. et al. A multifunctional core–shell nanoparticle for dendritic cell-based cancer immunotherapy. Nat. Nanotech. 6, 675–682 (2011).10.1038/nnano.2011.149 ↗
11. Cho, H. J. et al. Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism. Nat. Biotechnol. 18, 509–514 (2000).10.1038/75365 ↗
12. Bobisse, S., Foukas, P. G., Coukos, G. & Harari, A. Neoantigen-based cancer immunotherapy. Ann. Transl. Med. 4, 262–270 (2016).10.21037/atm.2016.06.17 ↗
13. Kim, J. et al. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat. Biotechnol. 33, 64–72 (2015).10.1038/nbt.3071 ↗
14. Song, W. J., Du, J. Z., Sun, T. M., Zhang, P. Z. & Wang, J. Gold nanoparticles capped with polyethyleneimine for enhanced siRNA delivery. Small 6, 239–246 (2010).10.1002/smll.200901513 ↗
15. Sakai, S., Yamada, Y., Yamaguchi, T., Ciach, T. & Kawakami, K. Surface immobilization of poly(ethyleneimine) and plasmid DNA on electrospun poly(L-lactic acid) fibrous mats using a layer-by-layer approach for gene delivery. J. Biomed. Mater. Res. A 88, 281–287 (2009).10.1002/jbm.a.31870 ↗
16. Oh, Y.-K. et al. Enhanced adjuvanticity of interleukin-2 plasmid DNA administered in polyethylenimine complexes. Vaccine 21, 2837–2843 (2003).10.1016/S0264-410X(03)00178-6 ↗
17. Mulens-Arias, V., Rojas, J. M., Pérez-Yagüe, S., Morales, M. P. & Barber, D. F. Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics. Biomaterials 52, 494–506 (2015).10.1016/j.biomaterials.2015.02.068 ↗
18. Wegmann, F. et al. Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. Nat. Biotechnol. 30, 883–888 (2012).10.1038/nbt.2344 ↗
19. Sheppard, N. C. et al. Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens. Int. Immunol. 26, 531–538 (2014).10.1093/intimm/dxu055 ↗
20. He, W. et al. Re-polarizing myeloid-derived suppressor cells (MDSCs) with cationic polymers for cancer immunotherapy. Sci. Rep. 6 (2016).10.1038/srep24506 ↗
21. Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847–856 (2008).10.1038/ni.1631 ↗
22. Eisenbarth, S. C., Colegio, O. R., O’Connor, W., Sutterwala, F. S. & Flavell, R. A. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453, 1122–1126 (2008).10.1038/nature06939 ↗
23. Vollmer, J. & Krieg, A. M. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv. Drug Deliv. Rev. 61, 195–204 (2009).10.1016/j.addr.2008.12.008 ↗
24. Bartkowiak, T. et al. Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+tumors when combined with an E6/E7 peptide vaccine. Proc. Natl Acad. Sci. USA 112, E5290–E5299 (2015).10.1073/pnas.1514418112 ↗
25. Chaturvedi, A. K. Beyond cervical cancer: burden of other HPV-related cancers among men and women. J. Adolesc. Health 46, S20–S26 (2010).10.1016/j.jadohealth.2010.01.016 ↗
26. Welters, M. J. et al. Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses. Sci. Transl. Med. 8, 334ra352 (2016).10.1126/scitranslmed.aad8307 ↗
27. Zwaveling, S. et al. Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J. Immunol. 169, 350–358 (2002).10.4049/jimmunol.169.1.350 ↗
28. van der Sluis, T. C. et al. Therapeutic peptide vaccine-induced CD8 T cells strongly modulate intratumoral macrophages required for tumor regression. Cancer Immunol. Res. 3, 1042–1051 (2015).10.1158/2326-6066.CIR-15-0052 ↗
29. Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature (2016).10.1038/nature18300 ↗
30. Kvistborg, P. et al. Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response. Sci. Transl. Med. 6, 254ra128 (2014).10.1126/scitranslmed.3008918 ↗
31. Li, W. A. et al. The effect of surface modification of mesoporous silica micro-rod scaffold on immune cell activation and infiltration. Biomaterials 83, 249–256 (2016).10.1016/j.biomaterials.2016.01.026 ↗
32. Kim, J. et al. Effect of pore structure of macroporous poly (lactide-co-glycolide) scaffolds on the in vivo enrichment of dendritic cells. ACS Appl. Mater. Interf. 6, 8505–8512 (2014).10.1021/am501376n ↗
33. Moynihan, K. D. et al. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat. Med. 22, 1402–1410 (2016).10.1038/nm.4200 ↗
34. Höpken, U. E. et al. The ratio between dendritic cells and T cells determines the outcome of their encounter: proliferation versus deletion. Eur. J. Immunol. 35, 2851–2863 (2005).10.1002/eji.200526298 ↗
35. Zhou, P. et al. In vivo discovery of immunotherapy targets in the tumor microenvironment. Nature 506, 52 (2014).10.1038/nature12988 ↗