Nanoliposome-Based Multi-Epitope Vaccine Targeting AFP, GPC3, and TERT Modulates Inflammatory Gene Expression in the Spleen: A Preclinical Study in a Murine Model of Hepatocellular Carcinoma
Archives of Advances in Biosciences,
Vol. 17 No. 1 (2026),
28 Ordibehesht 2026
,
Page 1-14
https://doi.org/10.22037/aab.v16i1.52005
Abstract
Background and Aim: Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited response to conventional immunotherapies. Multi-epitope vaccines targeting multiple tumor-associated antigens (TAAs) such as alpha-fetoprotein (AFP), glypican-3 (GPC3), and telomerase reverse transcriptase (TERT) offer a promising strategy to overcome immune evasion. However, peptide-based vaccines suffer from rapid degradation and poor delivery to antigen-presenting cells. This study aimed to develop a nanoliposomal vaccine encapsulating a bioinformatics-designed merged multi-epitope peptide derived from AFP, GPC3, and TERT, and evaluate its ability to modulate inflammatory gene expression in the spleen of immunized mice.
Methods: A merged peptide (PGLPDSALDINECLRGKKKDGARGGPPEAFTTSVRKKKKPEGLSPNLNRFLGDR) was designed using IEDB and NetMHCpan servers. Cationic nanoliposomes (DPPC:cholesterol:DSPE-PEG2000, 55:40:5 molar ratio) were prepared by thin-film hydration. Size, zeta potential, and peptide loading were characterized by DLS and BCA assay. Female BALB/c mice (n=24) were divided into four groups: PBS control, empty liposome, free peptide, and NLME vaccine. After three subcutaneous immunizations, splenic expression of IFN-γ, TNF-α, IL-6, IL-1β, and IL-10 was measured by qRT-PCR.
Results: Nanoliposomes exhibited mean size of 105±12 nm, zeta potential of +30.4±2.1 mV, and peptide loading efficiency of 89.4±3.2%. NLME vaccination significantly upregulated IFN-γ (5.67-fold, p<0.01), TNF-α (4.23-fold, p<0.01), IL-1β (2.98-fold, p<0.01), and IL-6 (2.12-fold, p<0.05), while downregulating IL-10 (0.42-fold, p<0.01) compared to controls.
Conclusion: The NLME vaccine induces a robust Th1-polarized inflammatory response in the spleen with high pro-inflammatory cytokine expression and suppressed IL-10, supporting its potential as an effective immunotherapy for HCC.
- Hepatocellular carcinoma
- nanoliposome
- multi epitope vaccine
- inflammatory cytokines
- spleen
How to Cite
References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021 May;71(3):209 249. (DOI: https://doi.org/10.3322/caac.21660) (PMID)
2. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nature Reviews Disease Primers. 2021 Mar;7(1):6. (DOI: https://doi.org/10.1038/s41572-020-00240-3) (PMID)
3. Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double blind, placebo controlled, phase 3 trial. Lancet. 2017 May;389(10064):56 66. (DOI: https://doi.org/10.1016/S0140-6736(16)32453-9) (PMID)
4. El Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open label, non comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 May;389(10088):2492 2502. (DOI: https://doi.org/10.1016/S0140-6736(17)31046-2) (PMID)
5. Saxena M, van der Burg SH, Melief CJM, Bhardwaj N. Therapeutic cancer vaccines. Nature Reviews Cancer. 2021 Jun;21(6):360 378. (DOI: https://doi.org/10.1038/s41568-021-00346-0) (PMID)
6. Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines. 2019 Feb;4:7. (DOI: https://doi.org/10.1038/s41541-019-0103-y) (PMID)
7. Butterfield LH, Ribas A, Dissette VB, Lee Y, Yang JQ, De la Rocha P, et al. A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha fetoprotein peptides. Clinical Cancer Research. 2006 May;12(9):2817 2825. (DOI: https://doi.org/10.1158/1078-0432.CCR-05-2405) (PMID)
8. Tsuchiya N, Yoshikawa T, Fujinami N, Saito K, Mizuno S, Sawada Y, et al. Immunological efficacy of glypican 3 peptide vaccine in patients with advanced hepatocellular carcinoma. OncoImmunology. 2017 Oct;6(10):e1346764. (DOI: https://doi.org/10.1080/2162402X.2017.1346764) (PMID)
9. Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Sakai A, Sakai Y, et al. Comparative analysis of various tumor associated antigens in patients with hepatocellular carcinoma. Cancer Science. 2011 Aug;102(8):1526 1532. (DOI: https://doi.org/10.1111/j.1349-7006.2011.01981.x) (PMID)
10. Duong S, Côté M, Labrie M, Pons M, Bordeleau E, Audet P, et al. Antigenic heterogeneity of hepatocellular carcinoma: Implications for immune based therapies. Journal of Hepatology. 2020 Apr;72(4):705 716. (DOI: https://doi.org/10.1016/j.jhep.2019.11.023) (PMID)
11. Li W, Joshi MD, Singhania S, Ramsey KH, Murthy AK. Multi epitope vaccine design using immunoinformatics against SARS CoV 2. Scientific Reports. 2020 Oct;10(1):18085. (DOI: https://doi.org/10.1038/s41598-020-74766-0) (PMID)
12. Negahdaripour M, Nezafat N, Ghasemi Y. A panoramic review and in silico analysis of IL 22 and IL 22 receptor: A new paradigm in immunology. International Journal of Peptide Research and Therapeutics. 2021 Mar;27(2):1185 1206. (DOI: https://doi.org/10.1007/s10989-020-10163-6) (PMID)
13. Moon JJ, Huang B, Irvine DJ. Engineering nano and microparticles to tune immunity. Advanced Materials. 2012 Jul;24(28):3724 3746. (DOI: https://doi.org/10.1002/adma.201200446) (PMID)
14. Alavi M, Hamidi M. Passive and active targeting in cancer therapy by liposomes and lipid nanoparticles. Drug Metabolism and Personalized Therapy. 2019;34(1). (DOI: https://doi.org/10.1515/dmpt-2018-0036) (PMID)
15. Tezgel Ö, Staufer U, Riechers D, Möschwitzer V, Engel R, Tovar GEM, et al. Impact of formulation and surface charge on the uptake of liposomes into dendritic cells. European Journal of Pharmaceutics and Biopharmaceutics. 2020 Jun;149:182 190. (DOI: https://doi.org/10.1016/j.ejpb.2020.02.008) (PMID)
16. Reddy ST, Rehor A, Schmoekel HG, Hubbell JA, Swartz MA. In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles. Journal of Controlled Release. 2006 May;112(1):26 34. (DOI: https://doi.org/10.1016/j.jconrel.2006.01.006) (PMID)
17. Lewis SM, Williams A, Eisenbarth SC. Structure and function of the immune system in the spleen. Science Immunology. 2019 Jan;4(33):eaau6085. (DOI: https://doi.org/10.1126/sciimmunol.aau6085) (PMID)
18. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer related inflammation. Nature. 2008 Jul;454(7203):436 444. (DOI: https://doi.org/10.1038/nature07205) (PMID)
19. Ikeda H, Old LJ, Schreiber RD. The roles of IFN γ in protection against tumor development and cancer immunoediting. Cytokine and Growth Factor Reviews. 2002 Apr;13(2):95 109. (DOI: https://doi.org/10.1016/S1359-6101(01)00038-7) (PMID)
20. Balkwill F. TNF α in promotion and progression of cancer. Cancer and Metastasis Reviews. 2006 Sep;25(3):409 416. (DOI: https://doi.org/10.1007/s10555-006-9005-3) (PMID)
21. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin 10 and the interleukin 10 receptor. Annual Review of Immunology. 2001 Apr;19:683 765. (DOI: https://doi.org/10.1146/annurev.immunol.19.1.683) (PMID)
22. Taniguchi K, Karin M. IL 6 and related cytokines as the critical lynchpins between inflammation and cancer. Seminars in Immunology. 2014 Feb;26(1):54 74. (DOI: https://doi.org/10.1016/j.smim.2014.01.001) (PMID)
23. Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nature Materials. 2017 Apr;16(4):489 496. (DOI: https://doi.org/10.1038/nmat4822) (PMID)
24. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real time quantitative PCR and the 2 ΔΔCt method. Methods. 2001 Dec;25(4):402 408. (DOI: https://doi.org/10.1006/meth.2001.1262) (PMID)
25. Butterfield LH. AFP: A new player in the immunology of hepatocellular carcinoma. Cellular and Molecular Immunology. 2012 Jul;9(4):286 288. (DOI: https://doi.org/10.1038/cmi.2012.23) (PMID)
26. Nakagawa H, Mizukoshi E, Kobayashi K, Kitahara M, Yamashita T, Sakai A, et al. Association between high avidity T cell responses to AFP and clinical features of patients with hepatocellular carcinoma. Journal of Hepatology. 2012 Mar;56(3):616 622. (DOI: https://doi.org/10.1016/j.jhep.2011.10.010) (PMID)
27. Sawada Y, Yoshikawa T, Ofuji K, Yoshimura M, Tsuchiya N, Takahashi M, et al. Phase II study of the GPC3 derived peptide vaccine in patients with advanced hepatocellular carcinoma. Cancer Science. 2017 May;108(5):1003 1009. (DOI: https://doi.org/10.1111/cas.13238) (PMID)
28. Zhang L, Wang Y, Tong X, Li Z, Chen L, Li F, et al. A multi epitope vaccine based on AFP, GPC3, and TERT elicits robust anti tumor immunity against hepatocellular carcinoma in a mouse model. OncoImmunology. 2021 Jan;10(1):1957602. (DOI: https://doi.org/10.1080/2162402X.2021.1957602) (PMID)
29. Sette A, Fikes J. Epitope based vaccines: An update on epitope identification, vaccine design and delivery. Current Opinion in Immunology. 2003 Aug;15(4):461 470. (DOI: https://doi.org/10.1016/S0952-7915(03)00080-8) (PMID)
30. Purcell AW, McCluskey J, Rossjohn J. More than one reason to rethink the use of peptides in vaccine design. Nature Reviews Drug Discovery. 2007 May;6(5):404 414. (DOI: https://doi.org/10.1038/nrd2224) (PMID)
31. Melief CJ, van der Burg SH. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nature Reviews Cancer. 2008 May;8(5):351 360. (DOI: https://doi.org/10.1038/nrc2373) (PMID)
32. Oussoren C, Zuidema J, Crommelin DJ, Storm G. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection: II. Influence of liposomal size, lipid composition and lipid dose. Biochimica et Biophysica Acta. 1997 Jul;1328(2):261 272. (DOI: https://doi.org/10.1016/S0005-2736(97)00117-0) (PMID)
33. Alving CR, Peachman KK, Rao M, Reed SG. Adjuvants for human vaccines. Current Opinion in Immunology. 2012 Jun;24(3):310 315. (DOI: https://doi.org/10.1016/j.coi.2012.03.008) (PMID)
34. Bachmann MF, Jennings GT. Vaccine delivery: A matter of size, geometry, kinetics and molecular patterns. Nature Reviews Immunology. 2010 Nov;10(11):787 796. (DOI: https://doi.org/10.1038/nri2868) (PMID)
35. Reddy ST, van der Vlies AJ, Simeoni E, Angeli V, Randolph GJ, O’Neil CP, et al. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nature Biotechnology. 2007 Oct;25(10):1159 1164. (DOI: https://doi.org/10.1038/nbt1332) (PMID)
36. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018 Feb;10(2):57. (DOI: https://doi.org/10.3390/pharmaceutics10020057) (PMID)
37. Foged C, Brodin B, Frokjaer S, Sundblad A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. International Journal of Pharmaceutics. 2005 Jun;298(2):315 322. (DOI: https://doi.org/10.1016/j.ijpharm.2005.03.035) (PMID)
38. Faham A, Altin JG. Antigen containing liposomes engrafted with flagellin related peptides are effective vaccines that can induce potent antitumor immunity and immunotherapeutic effect. Journal of Immunology. 2010 Aug;185(3):1744 1754. (DOI: https://doi.org/10.4049/jimmunol.1000404) (PMID)
39. Ahmed S, Parama D, Daimari E, Girisa S, Banik K, Harsha C, et al. Cationic liposome based vaccine for cancer immunotherapy. Journal of Controlled Release. 2022 Jun;346:1 20. (DOI: https://doi.org/10.1016/j.jconrel.2022.04.036) (PMID)
40. Traikia M, Warschawski DE, Recouvreur M, Cartaud J, Devaux PF. Formation of unilamellar vesicles by repetitive freeze thaw cycles: Characterization by electron microscopy and 31P NMR. European Biophysics Journal. 2000 Mar;29(3):184 195. (DOI: https://doi.org/10.1007/s002490050256) (PMID)
41. Crommelin DJ, Mastrobattista E, Storm G. Liposomes in the treatment of cancer. In: Crommelin DJ, Sindelar RD, Meibohm B, editors. Pharmaceutical Biotechnology. 4th ed. Cham: Springer; 2018:265 287. (LINK)
42. Schoenborn JR, Wilson CB. Regulation of interferon gamma during innate and adaptive immune responses. Advances in Immunology. 2007;96:41 101. (DOI: https://doi.org/10.1016/S0065-2776(07)96002-2) (PMID)
43. Seliger B, Ritz U, Ferrone S. Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation. International Journal of Cancer. 2006 Jan;118(2):279 286. (DOI: https://doi.org/10.1002/ijc.21312) (PMID)
44. Heink S, Ludwig D, Kloetzel PM, Krüger E. IFN gamma induced immune adaptation of the proteasome system is an accelerated and transient response. Proceedings of the National Academy of Sciences of the United States of America. 2005 Jun;102(26):9241 9246. (DOI: https://doi.org/10.1073/pnas.0501711102) (PMID)
45. Qin Z, Blankenstein T. A cancer vaccine that elicits a strong T cell response but no systemic inflammatory response. Cancer Research. 2000 Feb;60(3):738 745. (PMID)
46. Mantovani A, Sica A. Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Current Opinion in Immunology. 2010 Apr;22(2):231 237. (DOI: https://doi.org/10.1016/j.coi.2010.01.009) (PMID)
47. Liu Y, Wang C, Zhang S, Chen L, Zhang C, Yu Y, et al. Nanoliposome mediated multi epitope vaccine elicits potent antitumor immunity in melanoma model. Journal of Nanobiotechnology. 2022 Mar;20(1):112. (DOI: https://doi.org/10.1186/s12951-022-01318-2) (PMID)
48. Wang X, Li Y, Zhang H, Chen J, Liu Z, Zhao Y, et al. Liposomal AFP vaccine combined with anti PD 1 therapy improves survival in orthotopic HCC mice. Molecular Therapy. 2021 Apr;29(4):1485 1497. (DOI: https://doi.org/10.1016/j.ymthe.2020.12.023) (PMID)
49. Kaur R, Badea I. Liposomes as a vaccine delivery system: A review of the recent advances. Therapeutic Delivery. 2014 Dec;5(12):1301 1323. (DOI: https://doi.org/10.4155/tde.14.91) (PMID)
50. Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, Twyman Saint Victor C, et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell. 2016 Dec;167(6):1540 1554.e12. (DOI: https://doi.org/10.1016/j.cell.2016.11.022) (PMID)
51. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin induced serum factor that causes necrosis of tumors. Proceedings of the National Academy of Sciences of the United States of America. 1975 Sep;72(9):3666 3670. (DOI: https://doi.org/10.1073/pnas.72.9.3666) (PMID)
52. Micheau O, Tschopp J. Induction of TNF receptor I mediated apoptosis via two sequential signaling complexes. Cell. 2003 Jul;114(2):181 190. (DOI: https://doi.org/10.1016/S0092-8674(03)00521-X) (PMID)
53. Pober JS. Endothelial activation: intracellular signaling pathways. Arthritis Research. 2002;4(Suppl 3):S109 S116. (DOI: https://doi.org/10.1186/ar576) (PMID)
54. Karin M. Nuclear factor κB in cancer development and progression. Nature. 2006 May;441(7092):431 436. (DOI: https://doi.org/10.1038/nature04870) (PMID)
55. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of pro IL 1β. Molecular Cell. 2002 Aug;10(2):417 426. (DOI: https://doi.org/10.1016/S1097-2765(02)00599-3) (PMID)
56. Ben Sasson SZ, Wang J, Paul WE. CD4+ T cells: the prominent IL 1β producers in the spleen after LPS injection. Journal of Immunology. 2015 Feb;194(3):1042 1051. (DOI: https://doi.org/10.4049/jimmunol.1401349) (PMID)
57. Lee J, Nakayama T. The role of IL 1β in T cell differentiation and memory formation. International Immunology. 2019 Dec;31(12):785 791. (DOI: https://doi.org/10.1093/intimm/dxz047) (PMID)
58. Sharp FA, Ruane D, Claass B, Creagh E, Harris J, Malyala P, et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proceedings of the National Academy of Sciences of the United States of America. 2009 Jan;106(3):870 875. (DOI: https://doi.org/10.1073/pnas.0804897106) (PMID)
59. Naugler WE, Karin M. The wolf in sheep’s clothing: the role of interleukin 6 in immunity, inflammation and cancer. Trends in Molecular Medicine. 2008 Mar;14(3):109 119. (DOI: https://doi.org/10.1016/j.molmed.2007.12.007) (PMID)
60. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity. 2008 Apr;28(4):445 453. (DOI: https://doi.org/10.1016/j.immuni.2008.03.001) (PMID)
61. Curnow SJ, Scheel Toellner D, Jenkinson W, Raza K, Durrani Z, Faint JM, et al. Inhibition of T cell apoptosis in the rheumatoid synovium. Journal of Immunology. 2001 Feb;166(3):1952 1957. (DOI: https://doi.org/10.4049/jimmunol.166.3.1952) (PMID)
62. Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL 6 and TNF expression. Cell. 2010 Jan;140(2):197 208. (DOI: https://doi.org/10.1016/j.cell.2009.12.052) (PMID)
63. Kushner I, Rzewnicki D, Samols D. What does minor elevation of C reactive protein signify? The American Journal of Medicine. 2006 Feb;119(2):105.e17 105.e28. (DOI: https://doi.org/10.1016/j.amjmed.2005.06.057) (PMID)
64. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL 10 family of cytokines in inflammation and disease. Annual Review of Immunology. 2011 Apr;29:71 109. (DOI: https://doi.org/10.1146/annurev-immunol-031210-101312) (PMID)
65. Couper KN, Blount DG, Riley EM. IL 10: the master regulator of immunity to infection. Journal of Immunology. 2008 May;180(9):5771 5777. (DOI: https://doi.org/10.4049/jimmunol.180.9.5771) (PMID)
66. Hattori H, Okuda H, Ogata T, Saito A, Hano H. Prognostic significance of interleukin 10 in patients with hepatocellular carcinoma. Journal of Gastroenterology and Hepatology. 2007 Dec;22(12):2189 2194. (DOI: https://doi.org/10.1111/j.1440-1746.2006.04692.x) (PMID)
67. Wei J, Duramad O, Perng OA, Reiner SL, Liu YJ, Qin FX. Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of FoxP3+ regulatory T cells. Proceedings of the National Academy of Sciences of the United States of America. 2007 Nov;104(46):18169 18174. (DOI: https://doi.org/10.1073/pnas.0708808104) (PMID)
68. Saraiva M, O’Garra A. The regulation of IL 10 production by immune cells. Nature Reviews Immunology. 2010 Mar;10(3):170 181. (DOI: https://doi.org/10.1038/nri2711) (PMID)
69. Zhang Y, Chen K, Li Z, Wang H, Sun R, Zhang Q, et al. Liposomal alpha fetoprotein vaccine combined with CpG induces potent antitumor immunity against hepatocellular carcinoma. OncoTargets and Therapy. 2019;12:9605 9617. (DOI: https://doi.org/10.2147/OTT.S225171) (PMID)
70. Li J, Wang Y, Chen X, Liu Z, Zhang H, Wei L. Glypican 3 peptide loaded liposomes elicit strong CTL responses against hepatocellular carcinoma. Cancer Immunology, Immunotherapy. 2020 May;69(5):805 818. (DOI: https://doi.org/10.1007/s00262-020-02493-0) (PMID)
71. Zhao L, Zhang B, Jiang D, Chen Y. Multi antigen peptide mixture vaccine targeting AFP, GPC3 and TERT for hepatocellular carcinoma immunotherapy. Vaccines. 2021 Jul;9(7):728. (DOI: https://doi.org/10.3390/vaccines9070728) (PMID)
72. Lindblad EB. Freund’s complete and incomplete adjuvants. In: Schijns VEJC, O’Hagan DT, editors. Vaccine Adjuvants. 2nd ed. New York: Humana Press; 2017:1 10.[LINK]
73. Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal formulations in clinical use: an updated review. Pharmaceutics. 2017 Mar;9(2):12. (DOI: https://doi.org/10.3390/pharmaceutics9020012) (PMID)
74. Klein SL, Flanagan KL. Sex differences in immune responses. Nature Reviews Immunology. 2016 Oct;16(10):626 638. (DOI: https://doi.org/10.1038/nri.2016.90) (PMID)
75. Mebius RE, Kraal G. Structure and function of the spleen. Nature Reviews Immunology. 2005 Aug;5(8):606 616. (DOI: https://doi.org/10.1038/nri1669) (PMID)
76. Swartz MA. The physiology of the lymphatic system. Advanced Drug Delivery Reviews. 2001 Aug;50(1 2):3 20. (DOI: https://doi.org/10.1016/S0169-409X(01)00150-8) (PMID)
77. Rao DA, Forrest ML, Alani AW, Kwon GS, Robinson JR. Biodegradable PLGA particles for the sustained release of antigens and adjuvants. Journal of Controlled Release. 2018 Jun;276:122 134. (DOI: https://doi.org/10.1016/j.jconrel.2018.02.015) (PMID)
78. Fromen CA, Robbins GR, Shen TW, Kai MP, Ting JP, DeSimone JM. Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization. Proceedings of the National Academy of Sciences of the United States of America. 2015 Jan;112(2):488 493. (DOI: https://doi.org/10.1073/pnas.1422929112) (PMID)
79. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007 Sep;449(7161):419 426. (DOI: https://doi.org/10.1038/nature06175) (PMID)
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