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Cancer vaccines aimed at expanding the pool or increasing the activity of tumor-specific T cells against malignancies is an important immunotherapy modality that has been extensively pursued in the past decades. However, the clinical efficacy of cancer vaccines remains modest in comparison to other immunotherapies, such as checkpoint blockade and adoptive T cell therapy. This unsatisfactory performance is likely due to the suboptimal selection of tumor antigens for vaccine and inefficient delivery platform. Recently, vaccines designed to target cancer neoantigens have shown marked promise in both preclinical and early clinical studies. However, enormous challenges need to be overcome to develop a highly efficient and safe delivery strategy for targeting cancer vaccines to professional antigen-presenting cells and eliciting optimized immune response against cancers. To meet these challenges, biomaterials, particularly biomaterials that are designed to respond to certain environmental stimuli, termed as stimuli-responsive biomaterials, are being actively developed to precisely manipulate the trafficking and release of cancer vaccines in vivo for enhanced therapeutic efficacy and safety. In this mini review, we provide a brief overview of the recent advances in applying stimuli-responsive biomaterials in enhancing non-cellular cancer vaccines while focusing on the chemistry and material design with varied responsiveness. We also discuss the present challenges and opportunities in the field and provide a perspective for future directions.


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Engineering cancer vaccines using stimuli-responsive biomaterials

Show Author's information Yu Zhao1Yugang Guo1Li Tang1,2( )
Institute of Bioengineering)École polytechnique fédérale de Lausanne (EPFL)LausanneCH-1015Switzerland
Institute of Materials Science & EngineeringÉcole polytechnique fédérale de Lausanne (EPFL)LausanneCH-1015Switzerland

Abstract

Cancer vaccines aimed at expanding the pool or increasing the activity of tumor-specific T cells against malignancies is an important immunotherapy modality that has been extensively pursued in the past decades. However, the clinical efficacy of cancer vaccines remains modest in comparison to other immunotherapies, such as checkpoint blockade and adoptive T cell therapy. This unsatisfactory performance is likely due to the suboptimal selection of tumor antigens for vaccine and inefficient delivery platform. Recently, vaccines designed to target cancer neoantigens have shown marked promise in both preclinical and early clinical studies. However, enormous challenges need to be overcome to develop a highly efficient and safe delivery strategy for targeting cancer vaccines to professional antigen-presenting cells and eliciting optimized immune response against cancers. To meet these challenges, biomaterials, particularly biomaterials that are designed to respond to certain environmental stimuli, termed as stimuli-responsive biomaterials, are being actively developed to precisely manipulate the trafficking and release of cancer vaccines in vivo for enhanced therapeutic efficacy and safety. In this mini review, we provide a brief overview of the recent advances in applying stimuli-responsive biomaterials in enhancing non-cellular cancer vaccines while focusing on the chemistry and material design with varied responsiveness. We also discuss the present challenges and opportunities in the field and provide a perspective for future directions.

Keywords: nanoparticle, immune response, cancer vaccine, stimuli-responsive, biomaterial, lymph node targeting, cross-presentation

References(97)

1

Melero, I.; Gaudernack, G.; Gerritsen, W.; Huber, C.; Parmiani, G.; Scholl, S.; Thatcher, N.; Wagstaff, J.; Zielinski, C.; Faulkner, I. et al. Therapeutic vaccines for cancer: An overview of clinical trials. Nat. Rev. Clin. Oncol. 2014, 11, 509–524.

2

Cheever, M. A.; Higano, C. S. PROVENGE (sipuleucel-T) in prostate cancer: The first FDA-approved therapeutic cancer vaccine. Clin. Cancer Res. 2011, 17, 3520–3526.

3

Sahin, U.; Türeci, Ö. Personalized vaccines for cancer immunotherapy. Science 2018, 359, 1355–1360.

4

Zhu, G. Z.; Zhang, F. W.; Ni, Q. Q.; Niu, G.; Chen, X. Y. Efficient nanovaccine delivery in cancer immunotherapy. ACS Nano 2017, 11, 2387–2392.

5

Lu, Z. -R.; Qiao, P. Drug delivery in cancer therapy, Quo Vadis? Mol. Pharmaceutics, in press, DOI: 10.1021/acs.molpharmaceut.8b00037.

6

Langer, R. Drug delivery and targeting. Nature 1998, 392, 5–10.

7

Fenton, O. S.; Olafson, K. N.; Pillai, P. S.; Mitchell, M. J.; Langer, R. Advances in biomaterials for drug delivery. Adv. Mater. 2018, 30, 1705328.

8

Luo, Z. C.; Wu, Q. J.; Yang, C. B.; Wang, H. M.; He, T.; Wang, Y. Z.; Wang, Z. Y.; Chen, H.; Li, X. Y.; Gong, C. Y. et al. A powerful CD8+ T-cell stimulating D-tetra-peptide hydrogel as a very promising vaccine adjuvant. Adv. Mater. 2017, 29, 1601776.

9

Irvine, D. J.; Hanson, M. C.; Rakhra, K.; Tokatlian, T. Synthetic nanoparticles for vaccines and immunotherapy. Chem. Rev. 2015, 115, 11109–11146.

10

Mehta, N. K.; Moynihan, K. D.; Irvine, D. J. Engineering new approaches to cancer vaccines. Cancer Immunol. Res. 2015, 3, 836–843.

11

Guo, Y. G.; Lei, K. W.; Tang, L. Neoantigen vaccine delivery for personalized anticancer immunotherapy. Front. Immunol. 2018, 9, 1499.

12

Lu, Y.; Aimetti, A. A.; Langer, R.; Gu, Z. Bioresponsive materials. Nat. Rev. Mater. 2016, 2, 16075.

13

Senapati, S.; Mahanta, A. K.; Kumar, S.; Maiti, P. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct. Target. Ther. 2018, 3, 7.

14

Mura, S.; Nicolas, J.; Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 2013, 12, 991–1003.

15

Nakayama, M.; Akimoto, J.; Okano, T. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting. J. Drug Target. 2014, 22, 584–599.

16

Pardoll, D. M. Cancer vaccines. Nature 1998, 4, 525–531.

17

van der Burg, S. H.; Arens, R.; Ossendorp, F.; van Hall, T.; Melief, C. J. M. Vaccines for established cancer: Overcoming the challenges posed by immune evasion. Nat. Rev. Cancer 2016, 16, 219–233.

18

Halle, S.; Halle, O.; Förster, R. Mechanisms and dynamics of T cell-mediated cytotoxicity in vivo. Trends Immunol. 2017, 38, 432–443.

19

Garrido, F.; Aptsiauri, N.; Doorduijn, E. M.; Garcia Lora, A. M.; van Hall, T. The urgent need to recover MHC class Ⅰ in cancers for effective immunotherapy. Curr. Opin. Immunol. 2016, 39, 44–51.

20

Neefjes, J.; Jongsma, M. L. M.; Paul, P.; Bakke, O. Towards a systems understanding of MHC class Ⅰ and MHC class Ⅱ antigen presentation. Nat. Rev. Immunol. 2011, 11, 823–836.

21

Kawai, T.; Akira, S. The role of pattern-recognition receptors in innate immunity: Update on toll-like receptors. Nat. Immunol. 2010, 11, 373–384.

22

Sahdev, P.; Ochyl, L. J.; Moon, J. J. Biomaterials for nanoparticle vaccine delivery systems. Pharm. Res. 2014, 31, 2563–2582.

23

Supersaxo, A.; Hein, W. R.; Steffen, H. Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration. Pharm. Res. 1990, 7, 167–169.

24

Kaminskas, L. M.; Porter, C. J. H. Targeting the lymphatics using dendritic polymers (dendrimers). Adv. Drug Deliv. Rev. 2011, 63, 890–900.

25

Reddy, S. T.; Rehor, A.; Schmoekel, H. G.; Hubbell, J. A.; Swartz, M. A. In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles. J. Control. Release 2006, 112, 26–34.

26

Guo, Y. Y.; Wang, D.; Song, Q. L.; Wu, T. T.; Zhuang, X. T.; Bao, Y. L.; Kong, M.; Qi, Y.; Tan, S. W.; Zhang, Z. P. Erythrocyte membrane-enveloped polymeric nanoparticles as nanovaccine for induction of antitumor immunity against melanoma. ACS Nano 2015, 9, 6918–6933.

27

Wang, C.; Ye, Y. Q.; Hu, Q. Y.; Bellotti, A.; Gu, Z. Tailoring biomaterials for cancer immunotherapy: Emerging trends and future outlook. Adv. Mater. 2017, 29, 1606036.

28

Lynn, G. M.; Laga, R.; Darrah, P. A.; Ishizuka, A. S.; Balaci, A. J.; Dulcey, A. E.; Pechar, M.; Pola, R.; Gerner, M. Y.; Yamamoto, A. et al. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nat. Biotechnol. 2015, 33, 1201–1210.

29

Kwon, Y. J.; James, E.; Shastri, N.; Fréchet, J. M. J. In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles. Proc. Natl. Acad. Sci. USA 2005, 102, 18264–18268.

30

Duan, F.; Feng, X. C.; Yang, X. J.; Sun, W. T.; Jin, Y.; Liu, H. F.; Ge, K.; Li, Z. H.; Zhang, J. C. A simple and powerful co-delivery system based on pH-responsive metal-organic frameworks for enhanced cancer immunotherapy. Biomaterials 2017, 122, 23–33.

31

Foster, S.; Duvall, C. L.; Crownover, E. F.; Hoffman, A. S.; Stayton, P. S. Intracellular delivery of a protein antigen with an endosomal-releasing polymer enhances CD8 T-cell production and prophylactic vaccine efficacy. Bioconjug. Chem. 2010, 21, 2205–2212.

32

Wilson, J. T.; Keller, S.; Manganiello, M. J.; Cheng, C.; Lee, C. C.; Opara, C.; Convertine, A.; Stayton, P. S. pHresponsive nanoparticle vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides. ACS Nano 2013, 7, 3912–3925.

33

Yuba, E.; Kono, Y.; Harada, A.; Yokoyama, S.; Arai, M.; Kubo, K.; Kono, K. The application of pH-sensitive polymer-lipids to antigen delivery for cancer immunotherapy. Biomaterials 2013, 34, 5711–5721.

34

Liu, Q.; Chen, X. M.; Jia, J. L.; Zhang, W. F.; Yang, T. Y.; Wang, L. Y.; Ma, G. H. pH-responsive poly(D, L-lactic-coglycolic acid) nanoparticles with rapid antigen release behavior promote immune response. ACS Nano 2015, 9, 4925–4938.

35

Luo, M.; Wang, H.; Wang, Z. H.; Cai, H. C.; Lu, Z. G.; Li, Y.; Du, M. J.; Huang, G.; Wang, C. S.; Chen, X. et al. A STING-activating nanovaccine for cancer immunotherapy. Nat. Nanotechnol. 2017, 12, 648–654.

36

Morishita, M.; Takahashi, Y.; Nishikawa, M.; Ariizumi, R.; Takakura, Y. Enhanced class Ⅰ tumor antigen presentation via cytosolic delivery of exosomal cargos by tumor-cell-derived exosomes displaying a pH-sensitive fusogenic peptide. Mol. Pharmaceutics 2017, 14, 4079–4086.

37

Eby, J. K.; Dane, K. Y.; O'Neil, C. P.; Hirosue, S.; Swartz, M. A.; Hubbell, J. A. Polymer micelles with pyridyl disulfide-coupled antigen travel through lymphatics and show enhanced cellular responses following immunization. Acta Biomater. 2012, 8, 3210–3217.

38

Mochizuki, S.; Morishita, H.; Sakurai, K. Complex consisting of β-glucan and antigenic peptides with cleavage site for glutathione and aminopeptidases induces potent cytotoxic T lymphocytes. Bioconjugate Chem. 2017, 28, 2246–2253.

39

Kramer, K.; Shields, N. J.; Poppe, V.; Young, S. L.; Walker, G. F. Intracellular cleavable CpG oligodeoxynucleotideantigen conjugate enhances anti-tumor immunity. Mol. Ther. 2017, 25, 62–70.

40

Yang, Y.; Chen, Q. Q.; Wu, J. -P.; Kirk, T. B.; Xu, J. K.; Liu, Z. H.; Xue, W. Reduction-responsive codelivery system based on a metal–organic framework for eliciting potent cellular immune response. ACS Appl. Mater. Interfaces 2018, 10, 12463–12473.

41

Wang, K.; Wen, S. M.; He, L. H.; Li, A.; Li, Y.; Dong, H. Q.; Li, W.; Ren, T. B.; Shi, D. L.; Li, Y. Y. "Minimalist" nanovaccine constituted from near whole antigen for cancer immunotherapy. ACS Nano 2018, 12, 6398–6409.

42

Håkerud, M.; Waeckerle-Men, Y.; Selbo, P. K.; Kündig, T. M.; Høgset, A.; Johansen, P. Intradermal photosensitisation facilitates stimulation of MHC class-I restricted CD8 T-cell responses of co-administered antigen. J. Control. Release 2014, 174, 143–150.

43

Hjálmsdóttir, á.; Bühler, C.; Vonwil, V.; Roveri, M.; Håkerud, M.; Wäckerle-Men, Y.; Gander, B.; Johansen, P. Cytosolic delivery of liposomal vaccines by means of the concomitant photosensitization of phagosomes. Mol. Pharmaceutics 2016, 13, 320–329.

44

Zhang, C. N.; Zhang, J.; Shi, G. N.; Song, H. J.; Shi, S. B.; Zhang, X. Y.; Huang, P. S.; Wang, Z. H.; Wang, W. W.; Wang, C. et al. A light responsive nanoparticle-based delivery system using pheophorbide A graft polyethylenimine for dendritic cell-based cancer immunotherapy. Mol. Pharmaceutics 2017, 14, 1760–1770.

45

Cao, F. Q.; Yan, M. M.; Liu, Y. J.; Liu, L. X.; Ma, G. L. Photothermally controlled MHC class Ⅰ restricted CD8+ T-cell responses elicited by hyaluronic acid decorated gold nanoparticles as a vaccine for cancer immunotherapy. Adv. Healthc. Mater. 2018, 7, 1701439.

46

Un, K.; Kawakami, S.; Suzuki, R.; Maruyama, K.; Yamashita, F.; Hashida, M. Suppression of melanoma growth and metastasis by DNA vaccination using an ultrasound-responsive and mannose-modified gene carrier. Mol. Pharmaceutics 2011, 8, 543–554.

47

Yoshida, M.; Kawakami, S.; Kono, Y.; Un, K.; Higuchi, Y.; Maruyama, K.; Yamashita, F.; Hashida, M. Enhancement of the anti-tumor effect of DNA vaccination using an ultrasoundresponsive mannose-modified gene carrier in combination with doxorubicin-encapsulated PEGylated liposomes. Int. J. Pharm. 2014, 475, 401–407.

48

Reddy, S. T.; van der Vlies, A. J.; Simeoni, E.; Angeli, V.; Randolph, G. J.; O'Neil, C. P.; Lee, L. K.; Swartz, M. A.; Hubbell, J. A. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat. Biotechnol. 2007, 25, 1159–1164.

49

Liu, H. P.; Moynihan, K. D.; Zheng, Y. R.; Szeto, G. L.; Li, A. V; Huang, B.; van Egeren, D. S.; Park, C.; Irvine, D. J. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 2014, 507, 519–522.

50

Jewell, C. M.; Bustamante López, S. C.; Irvine, D. J. In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles. Proc. Natl. Acad. Sci. USA 2011, 108, 15745–15750.

51

Trombetta, E. S.; Ebersold, M.; Garrett, W.; Pypaert, M.; Mellman, I. Activation of lysosomal function during dendritic cell maturation. Science. 2003, 299, 1400–1403.

52

Overly, C. C.; Lee, K. D.; Berthiaume, E.; Hollenbeck, P. J. Quantitative measurement of intraorganelle pH in the endosomal-lysosomal pathway in neurons by using ratiometric imaging with pyranine. Proc. Natl. Acad. Sci. USA 1995, 92, 3156–3160.

53

Murthy, N.; Thng, Y. X.; Schuck, S.; Xu, M. C.; Fréchet, J. M. J. A novel strategy for encapsulation and release of proteins: Hydrogels and microgels with acid-labile acetal cross-linkers. J. Am. Chem. Soc. 2002, 124, 12398–12399.

54

Murthy, N.; Xu, M. C.; Schuck, S.; Kunisawa, J.; Shastri, N.; Fréchet, J. M. J. A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels. Proc. Natl. Acad. Sci. USA 2003, 100, 4995–5000.

55

Cohen, J. A.; Beaudette, T. T.; Tseng, W. W.; Bachelder, E. M.; Mende, I.; Engleman, E. G.; Fréchet, J. M. J. T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: The effect of particle size. Bioconjug. Chem. 2009, 20, 111–119.

56

Bachelder, E. M.; Beaudette, T. T.; Broaders, K. E.; Paramonov, S. E.; Dashe, J.; Fréchet, J. M. J. Acid-degradable polyurethane particles for protein-based vaccines: Biological evaluation and in vitro analysis of particle degradation products. Mol. Pharmaceutics 2008, 5, 876–884.

57

Ruff, L. E.; Mahmoud, E. A.; Sankaranarayanan, J.; Morachis, J. M.; Katayama, C. D.; Corr, M.; Hedrick, S. M.; Almutairi, A. Antigen-loaded pH-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies. Integr. Biol. 2013, 5, 195–203.

58

Nuhn, L.; Vanparijs, N.; De Beuckelaer, A.; Lybaert, L.; Verstraete, G.; Deswarte, K.; Lienenklaus, S.; Shukla, N. M.; Salyer, A. C. D.; Lambrecht, B. N. et al. pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation. Proc. Natl. Acad. Sci. USA 2016, 113, 8098–8103.

59

van Herck, S.; van Hoecke, L.; Louage, B.; Lybaert, L.; De Coen, R.; Kasmi, S.; Esser-Kahn, A. P.; David, S. A.; Nuhn, L.; Schepens, B. et al. Transiently thermoresponsive acetal polymers for safe and effective administration of amphotericin B as a vaccine adjuvant. Bioconjug. Chem. 2018, 29, 748–760.

60

Magarian Blander, J.; Medzhitov, R. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 2006, 440, 808–812.

61

Maier, K.; Wagner, E. Acid-labile traceless click linker for protein transduction. J. Am. Chem. Soc. 2012, 134, 10169–10173.

62

Gupta, P.; Vermani, K.; Garg, S. Hydrogels: From controlled release to pH-responsive drug delivery. Drug Discov. Today 2002, 7, 569–579.

63

van der Maaden, K.; Varypataki, E. M.; Romeijn, S.; Ossendorp, F.; Jiskoot, W.; Bouwstra, J. Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbuminspecific antibody and T-cell responses in mice. Eur. J. Pharm. Biopharm. 2014, 88, 310–315.

64

Tirrell, D. A.; Takigawa, D. Y.; Seki, K. pH sensitization of phospholipid vesicles via complexation with synthetic poly(carboxylic acid). Ann. N. Y. Acad. Sci. 1985, 446, 237–248.

65

Flanary, S.; Hoffman, A. S.; Stayton, P. S. Antigen delivery with poly(propylacrylic acid) conjugation enhances MHC-1 presentation and T-cell activation. Bioconjugate Chem. 2009, 20, 241–248.

66

Keller, S.; Wilson, J. T.; Patilea, G. I.; Kern, H. B.; Convertine, A. J.; Stayton, P. S. Neutral polymer micelle carriers with pH-responsive, endosome-releasing activity modulate antigen trafficking to enhance CD8+ T cell responses. J. Control. Release 2014, 191, 24–33.

67

Yuba, E.; Harada, A.; Sakanishi, Y.; Kono, K. Carboxylated hyperbranched poly(glycidol)s for preparation of pH-sensitive liposomes. J. Control. Release 2011, 149, 72–80.

68

Arab, A.; Behravan, J.; Razazan, A.; Gholizadeh, Z.; Nikpoor, A. R.; Barati, N.; Mosaffa, F.; Badiee, A.; Jaafari, M. R. A nano-liposome vaccine carrying E75, a HER-2/neu-derived peptide, exhibits significant antitumour activity in mice. J. Drug Target. 2018, 26, 365–372.

69

Yuba, E. Design of pH-sensitive polymer-modified liposomes for antigen delivery and their application in cancer immunotherapy. Polym. J. 2016, 48, 761–771.

70

Yuba, E.; Sakaguchi, N.; Kanda, Y.; Miyazaki, M.; Koiwai, K. pH-responsive micelle-based cytoplasmic delivery system for induction of cellular immunity. Vaccines 2017, 5, 41.

71

Hatakeyama, H.; Ito, E.; Akita, H.; Oishi, M.; Nagasaki, Y.; Futaki, S.; Harashima, H. A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. J. Control. Release 2009, 139, 127–132.

72

Li, W. J.; Nicol, F.; Szoka, F. C. GALA: A designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Adv. Drug Deliv. Rev. 2004, 56, 967–985.

73

Moon, J. J.; Suh, H.; Bershteyn, A.; Stephan, M. T.; Liu, H. P.; Huang, B.; Sohail, M.; Luo, S.; Ho Um, S.; Khant, H. et al. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat. Mater. 2011, 10, 243–251.

74

Qiu, L. P.; Valente, M.; Dolen, Y.; Jäger, E.; ter Beest, M.; Zheng, L. Y.; Figdor, C. G.; Verdoes, M. Endolysosomalescape nanovaccines through adjuvant-induced tumor antigen assembly for enhanced effector CD8+ T cell activation. Small 2018, 14, 1703539.

75

Boussif, O.; Lezoualc'h, F.; Zanta, M. A.; Mergny, M. D.; Scherman, D.; Demeneix, B.; Behr, J. P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proc. Natl. Acad. Sci. USA 1995, 92, 7297–7301.

76

Ma, X. P.; Wang, Y. G.; Zhao, T.; Li, Y.; Su, L. C.; Wang, Z. H.; Huang, G.; Sumer, B. D.; Gao, J. M. Ultra-pH-sensitive nanoprobe library with broad pH tunability and fluorescence emissions. J. Am. Chem. Soc. 2014, 136, 11085–11092.

77

López-Mirabal, H. R.; Winther, J. R. Redox characteristics of the eukaryotic cytosol. Biochim. Biophys. Acta -Mol. Cell Res. 2008, 1783, 629–640.

78

Bearinger, J. P.; Terrettaz, S.; Michel, R.; Tirelli, N.; Vogel, H.; Textor, M.; Hubbell, J. A. Chemisorbed poly(propylene sulphide)-based copolymers resist biomolecular interactions. Nat. Mater. 2003, 2, 259–264.

79

Li, D. D.; Sun, F. L.; Bourajjaj, M.; Chen, Y. N.; Pieters, E. H.; Chen, J.; van den Dikkenberg, J. B.; Lou, B.; Camps, M. G. M.; Ossendorp, F. et al. Strong in vivo antitumor responses induced by an antigen immobilized in nanogels via reducible bonds. Nanoscale 2016, 8, 19592–19604.

80

Go, Y. M.; Jones, D. P. Redox compartmentalization in eukaryotic cells. Biochim. Biophys. Acta -Gen. Subj. 2008, 1780, 1273–1290.

81

Håkerud, M.; Selbo, P. K.; Waeckerle-Men, Y.; Contassot, E.; Dziunycz, P.; Kündig, T. M.; Høgset, A.; Johansen, P. Photosensitisation facilitates cross-priming of adjuvant-free protein vaccines and stimulation of tumour-suppressing CD8 T cells. J. Control. Release 2015, 198, 10–17.

82

Weissleder, R.; Ntziachristos, V. Shedding light onto live molecular targets. Nat. Med. 2003, 9, 123–128.

83

Ji, Y.; Zhao, J. H.; Chu, C. C. Enhanced MHC-I antigen presentation from the delivery of ovalbumin by lightfacilitated biodegradable poly(ester amide)s nanoparticles. J. Mater. Chem. B 2018, 6, 1930–1942.

84

Hu, Q. Y.; Katti, P. S.; Gu, Z. Enzyme-responsive nanomaterials for controlled drug delivery. Nanoscale 2014, 6, 12273–12286.

85

Balint, R.; Cassidy, N. J.; Cartmell, S. H. Conductive polymers: Towards a smart biomaterial for tissue engineering. Acta Biomater. 2014, 10, 2341–2353.

86

Zhang, Y. Q.; Yu, J. C.; Bomba, H. N.; Zhu, Y.; Gu, Z. Mechanical force-triggered drug delivery. Chem. Rev. 2016, 116, 12536–12563.

87

Ramsay, J. D.; Williams, C. L.; Simko, E. Fatal adverse pulmonary reaction in calves after inadvertent intravenous vaccination. Vet. Pathol. 2005, 42, 492–495.

88

Reichmuth, A. M.; Oberli, M. A.; Jaklenec, A.; Langer, R.; Blankschtein, D. mRNA vaccine delivery using lipid nanoparticles. Ther. Deliv 2016, 7, 319–334.

89

Zhang, L.; Wang, W.; Wang, S. X. Effect of vaccine administration modality on immunogenicity and efficacy. Expert Rev. Vaccines 2015, 14, 1509–1523.

90

Broos, K.; van der Jeught, K.; Puttemans, J.; Goyvaerts, C.; Heirman, C.; Dewitte, H.; Verbeke, R.; Lentacker, I.; Thielemans, K.; Breckpot, K. Particle-mediated intravenous delivery of antigen mRNA results in strong antigen-specific T-cell responses despite the induction of type I interferon. Mol. Ther. Nucleic Acids 2016, 5, e326.

91

Kranz, L. M.; Diken, M.; Haas, H.; Kreiter, S.; Loquai, C.; Reuter, K. C.; Meng, M.; Fritz, D.; Vascotto, F.; Hefesha, H. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 2016, 534, 396–401.

92

Nelson, B. H. CD20+ B cells: The other tumor-infiltrating lymphocytes. J. Immunol. 2010, 185, 4977–4982.

93

Germain, C.; Gnjatic, S.; Tamzalit, F.; Knockaert, S.; Remark, R.; Goc, J.; Lepelley, A.; Becht, E.; Katsahian, S.; Bizouard, G. et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. Am. J. Respir. Crit. Care Med. 2014, 189, 832–844.

94

Riemer, A. B.; Untersmayr, E.; Knittelfelder, R.; Duschl, A.; Pehamberger, H.; Zielinski, C. C.; Scheiner, O.; Jensen-Jarolim, E. Active induction of tumor-specific IgE antibodies by oral mimotope vaccination. Cancer Res. 2007, 67, 3406–3412.

95

Hartmann, C.; Müller, N.; Blaukat, A.; Koch, J.; Benhar, I.; Wels, W. S. Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response. Oncogene 2010, 29, 4517–4527.

96

Brämswig, K. H.; Knittelfelder, R.; Gruber, S.; Untersmayr, E.; Riemer, A. B.; Szalai, K.; Horvat, R.; Kammerer, R.; Zimmermann, W.; Zielinski, C. C. et al. Immunization with mimotopes prevents growth of carcinoembryonic antigen positive tumors in BALB/c mice. Clin Cancer Res. 2007, 13, 6501–6509.

97

Ng, P. P.; Jia, M.; Patel, K. G.; Brody, J. D.; Swartz, J. R.; Levy, S.; Levy, R. A vaccine directed to B cells and produced by cell-free protein synthesis generates potent antilymphoma immunity. Proc. Natl. Acad. Sci. USA 2012, 109, 14526–14531.

Publication history
Copyright
Acknowledgements

Publication history

Received: 26 May 2018
Revised: 27 July 2018
Accepted: 28 July 2018
Published: 28 August 2018
Issue date: October 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Acknowledgements

Acknowledgements

This work was supported in part by the Foundation Pierre Mercier pour la science, ISREC Foundation with a donation from the Bateman Foundation, Swiss National Science Foundation (Project grant 315230_173243), Novartis Foundation for medical-biological Research (17A058), and the École polytechnique fédérale de Lausanne (EPFL).

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