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Cited by 16Immunotherapy and Immune Responsesvaccines and immunoinformatics approachesT-cell and B-cell Immunology

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Targeting Cross-Presentation as a Route to Improve the Efficiency of Peptide-Based Cancer Vaccines

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Wylie, Ben, Ong, Ferrer, Belhoul-Fakir, Hanane, Priebatsch, Kristin, Bogdawa, Heique, Stirnweiss, Anja, Watt, Paul, Cunningham, Paula, Stone, Shane R., Waithman, Jason·2021·Cancers
DOI 10.3390/cancers13246189PMC PMC8699136
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Abstract

Cross-presenting dendritic cells (DC) offer an attractive target for vaccination due to their unique ability to process exogenous antigens for presentation on MHC class I molecules. Recent reports have established that these DC express unique surface receptors and play a critical role in the initiation of anti-tumor immunity, opening the way for the development of vaccination strategies specifically targeting these cells. This study investigated whether targeting cross-presenting DC by two complementary mechanisms could improve vaccine effectiveness, in both a viral setting and in a murine melanoma model. Our novel vaccine construct contained the XCL1 ligand, to target uptake to XCR1+ cross-presenting DC, and a cell penetrating peptide (CPP) with endosomal escape properties, to enhance antigen delivery into the cross-presentation pathway. Using a prime-boost regimen, we demonstrated robust expansion of antigen-specific T cells following vaccination with our CPP-linked peptide vaccine and protective immunity against HSV-1 skin infection, where vaccine epitopes were natively expressed by the virus. Additionally, our novel vaccination strategy slowed tumor outgrowth in a B16 murine melanoma model, compared to adjuvant only controls, suggesting antigen-specific anti-tumor immunity was generated following vaccination. These findings suggest that novel strategies to target the antigen cross-presentation pathway in DC may be beneficial for the generation of anti-tumor immunity.

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  1. Hodi, 2010, Improved Survival with Ipilimumab in Patients with Metastatic Melanoma, N. Engl. J. Med., 363, 711, 10.1056/NEJMoa1003466 · DOI · Paper page
  2. Larkin, 2015, Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma, N. Engl. J. Med., 373, 23, 10.1056/NEJMoa1504030 · DOI · Paper page
  3. Gandhi, 2018, Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer, N. Engl. J. Med., 378, 2078, 10.1056/NEJMoa1801005 · DOI · Paper page
  4. Dudley, 2013, Randomized Selection Design Trial Evaluating CD8+-Enriched Versus Unselected Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy for Patients with Melanoma, J. Clin. Oncol., 31, 2152, 10.1200/JCO.2012.46.6441 · DOI
  5. Maude, 2015, CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia, Blood, 125, 4017, 10.1182/blood-2014-12-580068 · DOI
  6. Rosenberg, 2015, Adoptive cell transfer as personalized immunotherapy for human cancer, Science, 348, 62, 10.1126/science.aaa4967 · DOI
  7. Yarchoan, 2017, Targeting neoantigens to augment antitumour immunity, Nat. Rev. Cancer, 17, 209, 10.1038/nrc.2016.154 · DOI · Paper page
  8. Chang, 2020, The hypoxic tumour microenvironment: A safe haven for immunosuppressive cells and a therapeutic barrier to overcome, Cancer Lett., 487, 34, 10.1016/j.canlet.2020.05.011 · DOI
  9. Bonaventura, 2019, Cold Tumors: A Therapeutic Challenge for Immunotherapy, Front. Immunol., 10, 168, 10.3389/fimmu.2019.00168 · DOI
  10. Chen, 2013, Oncology Meets Immunology: The Cancer-Immunity Cycle, Immunity, 39, 1, 10.1016/j.immuni.2013.07.012 · DOI · Paper page
  11. Hollingsworth, 2019, Turning the corner on therapeutic cancer vaccines, NPJ Vaccines, 4, 7, 10.1038/s41541-019-0103-y · DOI · Paper page
  12. Banchereau, 2017, Cancer vaccines on the move, Nat. Rev. Clin. Oncol., 15, 9, 10.1038/nrclinonc.2017.149 · DOI
  13. Hoffmann, 2018, A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery, Sci. Rep., 8, 12538, 10.1038/s41598-018-30790-2 · DOI
  14. Tornesello, A.L., Tagliamonte, M., Tornesello, M.L., Buonaguro, F.M., and Buonaguro, L. (2020). Nanoparticles to Improve the Efficacy of Peptide-Based Cancer Vaccines. Cancers, 12. · DOI
  15. Gouttefangeas, 2018, Personalized cancer vaccines: Adjuvants are important, too, Cancer Immunol. Immunother., 67, 1911, 10.1007/s00262-018-2158-4 · DOI
  16. Vansteenkiste, 2013, Adjuvant MAGE-A3 Immunotherapy in Resected Non–Small-Cell Lung Cancer: Phase II Randomized Study Results, J. Clin. Oncol., 31, 2396, 10.1200/JCO.2012.43.7103 · DOI
  17. Lee, 2014, Melanoma Vaccines: Mixed past, promising future, Surg. Clin. N. Am., 94, 1017, 10.1016/j.suc.2014.07.005 · DOI
  18. Rini, 2016, IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): A multicentre, open-label, randomised, controlled, phase 3 trial, Lancet Oncol., 17, 1599, 10.1016/S1470-2045(16)30408-9 · DOI
  19. Zhao, 2019, Safety and Efficacy of Therapeutic Cancer Vaccines Alone or in Combination with Immune Checkpoint Inhibitors in Cancer Treatment, Front. Pharmacol., 10, 1184, 10.3389/fphar.2019.01184 · DOI
  20. Whitehead, 2021, What does the success of mRNA vaccines tell us about the future of biological therapeutics?, Cell Syst., 12, 757, 10.1016/j.cels.2021.07.005 · DOI
  21. Ott, 2017, An immunogenic personal neoantigen vaccine for patients with melanoma, Nature, 547, 217, 10.1038/nature22991 · DOI · Paper page
  22. Sahin, 2017, Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer, Nature, 547, 222, 10.1038/nature23003 · DOI · Paper page
  23. Bhardwaj, 2020, Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets, Nat. Rev. Cancer, 1, 1204, 10.1038/s43018-020-00143-y · DOI
  24. Kreiter, 2011, FLT3 Ligand Enhances the Cancer Therapeutic Potency of Naked RNA Vaccines, Cancer Res., 71, 6132, 10.1158/0008-5472.CAN-11-0291 · DOI · Paper page
  25. Gordy, 2016, Fusion of the dendritic cell-targeting chemokine MIP3α to melanoma antigen Gp100 in a therapeutic DNA vaccine significantly enhances immunogenicity and survival in a mouse melanoma model, J. Immunother. Cancer, 4, 96, 10.1186/s40425-016-0189-y · DOI
  26. Banchereau, 2000, Immunobiology of Dendritic Cells, Annu. Rev. Immunol., 18, 767, 10.1146/annurev.immunol.18.1.767 · DOI
  27. Joffre, 2012, Cross-presentation by dendritic cells, Nat. Rev. Immunol., 12, 557, 10.1038/nri3254 · DOI
  28. Wculek, 2020, Dendritic cells in cancer immunology and immunotherapy, Nat. Rev. Immunol., 20, 7, 10.1038/s41577-019-0210-z · DOI
  29. Salmon, 2016, Expansion and Activation of CD103+ Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition, Immunity, 44, 924, 10.1016/j.immuni.2016.03.012 · DOI
  30. Bachem, 2012, Expression of XCR1 Characterizes the Batf3-Dependent Lineage of Dendritic Cells Capable of Antigen Cross-Presentation, Front. Immunol., 3, 214, 10.3389/fimmu.2012.00214 · DOI
  31. Hartung, 2014, Induction of Potent CD8 T Cell Cytotoxicity by Specific Targeting of Antigen to Cross-Presenting Dendritic Cells In Vivo via Murine or Human XCR, J. Immunol., 194, 1069, 10.4049/jimmunol.1401903 · DOI
  32. Fossum, 2014, Vaccine molecules targeting Xcr1 on cross-presenting DCs induce protective CD8+T-cell responses against influenza virus, Eur. J. Immunol., 45, 624, 10.1002/eji.201445080 · DOI
  33. Fossum, 2020, Targeting Antigens to Different Receptors on Conventional Type 1 Dendritic Cells Impacts the Immune Response, J. Immunol., 205, 661, 10.4049/jimmunol.1901119 · DOI
  34. Zehner, 2015, The Translocon Protein Sec61 Mediates Antigen Transport from Endosomes in the Cytosol for Cross-Presentation to CD8+ T Cells, Immunity, 42, 850, 10.1016/j.immuni.2015.04.008 · DOI
  35. Malnati, 1992, Processing pathways for presentation of cytosolic antigen to MHC class II-restricted T cells, Nature, 357, 702, 10.1038/357702a0 · DOI
  36. Shen, 2004, Important Role of Cathepsin S in Generating Peptides for TAP-Independent MHC Class I Crosspresentation In Vivo, Immunity, 21, 155, 10.1016/j.immuni.2004.07.004 · DOI
  37. 2016, Intracellular recycling and cross-presentation by MHC class I molecules, Immunol. Rev., 272, 80, 10.1111/imr.12424 · DOI
  38. Segura, 2009, Different cross-presentation pathways in steady-state and inflammatory dendritic cells, Proc. Natl. Acad. Sci. USA, 106, 20377, 10.1073/pnas.0910295106 · DOI
  39. Milletti, 2012, Cell-penetrating peptides: Classes, origin, and current landscape, Drug Discov. Today, 17, 850, 10.1016/j.drudis.2012.03.002 · DOI
  40. Teo, 2021, Unravelling cytosolic delivery of cell penetrating peptides with a quantitative endosomal escape assay, Nat. Commun., 12, 1, 10.1038/s41467-021-23997-x · DOI
  41. Kim, 2008, Recruitment of Rab27a to Phagosomes Controls Microbial Antigen Cross-Presentation by Dendritic Cells, Infect. Immun., 76, 5373, 10.1128/IAI.01044-08 · DOI
  42. Savina, 2009, The Small GTPase Rac2 Controls Phagosomal Alkalinization and Antigen Crosspresentation Selectively in CD8+ Dendritic Cells, Immunity, 30, 544, 10.1016/j.immuni.2009.01.013 · DOI
  43. Nencioni, 2008, Crosspresentation: A matter of pH, Blood, 112, 4368, 10.1182/blood-2008-08-175703 · DOI
  44. Li, 2013, Structural Analysis and Optimization of the Covalent Association between SpyCatcher and a Peptide Tag, J. Mol. Biol., 426, 309, 10.1016/j.jmb.2013.10.021 · DOI
  45. Mueller, 2002, Characterization of two TCR transgenic mouse lines specific for herpes simplex virus, Immunol. Cell Biol., 80, 156, 10.1046/j.1440-1711.2002.01071.x · DOI
  46. Ayers, 2003, Herpes Simplex Virus-Specific CD8+T Cells can Clear Established Lytic Infections from Skin and Nerves and Can Partially Limit the Early Spread of Virus after Cutaneous Inoculation, J. Immunol., 172, 392
  47. Yang, 2006, Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging, Proc. Natl. Acad. Sci. USA, 103, 13872, 10.1073/pnas.0601455103 · DOI
  48. Austin, 2005, Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates, Proc. Natl. Acad. Sci. USA, 102, 17987, 10.1073/pnas.0509035102 · DOI
  49. Park, 2017, Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells, NPJ Vaccines, 2, 31, 10.1038/s41541-017-0033-5 · DOI
  50. Caminschi, 2008, The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement, Blood, 112, 3264, 10.1182/blood-2008-05-155176 · DOI
  51. Kamphorst, 2010, Route of Antigen Uptake Differentially Impacts Presentation by Dendritic Cells and Activated Monocytes, J. Immunol., 185, 3426, 10.4049/jimmunol.1001205 · DOI
  52. Birkholz, 2010, Targeting of DEC-205 on human dendritic cells results in efficient MHC class II–restricted antigen presentation, Blood, 116, 2277, 10.1182/blood-2010-02-268425 · DOI
  53. Idoyaga, 2011, Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A, Proc. Natl. Acad. Sci. USA, 108, 2384, 10.1073/pnas.1019547108 · DOI
  54. Tullett, 2016, Targeting CLEC9A delivers antigen to human CD141+ DC for CD4+ and CD8+T cell recognition, JCI Insight, 1, e87102, 10.1172/jci.insight.87102 · DOI
  55. Fehres, 2013, Skin-Resident Antigen-Presenting Cells: Instruction Manual for Vaccine Development, Front. Immunol., 4, 157, 10.3389/fimmu.2013.00157 · DOI
  56. Braun, 2019, Furin-mediated protein processing in infectious diseases and cancer, Clin. Transl. Immunol., 8, e1073, 10.1002/cti2.1073 · DOI
  57. Frankel, 1988, Cellular uptake of the tat protein from human immunodeficiency virus, Cell, 55, 1189, 10.1016/0092-8674(88)90263-2 · DOI
  58. Fischer, 2000, Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector Penetratin, J. Pept. Res., 55, 163, 10.1034/j.1399-3011.2000.00163.x · DOI
  59. Marchione, 2014, ZEBRA cell-penetrating peptide as an efficient delivery system in Candida albicans, Biotechnol. J., 9, 1088, 10.1002/biot.201300505 · DOI
  60. Wu, 2019, Cell-Penetrating Peptide Enhanced Antigen Presentation for Cancer Immunotherapy, Bioconjug. Chem., 30, 2115, 10.1021/acs.bioconjchem.9b00245 · DOI
  61. Tacken, 2008, No Advantage of Cell-Penetrating Peptides over Receptor-Specific Antibodies in Targeting Antigen to Human Dendritic Cells for Cross-Presentation, J. Immunol., 180, 7687, 10.4049/jimmunol.180.11.7687 · DOI
  62. Derouazi, 2015, Novel Cell-Penetrating Peptide-Based Vaccine Induces Robust CD4+ and CD8+ T Cell–Mediated Antitumor Immunity, Cancer Res., 75, 3020, 10.1158/0008-5472.CAN-14-3017 · DOI
  63. Belnoue, 2016, Enhancing Antitumor Immune Responses by Optimized Combinations of Cell-penetrating Peptide-based Vaccines and Adjuvants, Mol. Ther., 24, 1675, 10.1038/mt.2016.134 · DOI
  64. Belnoue, E., Mayol, J.-F., Carboni, S., Besson, W.D.B., Dupuychaffray, E., Nelde, A., Stevanovic, S., Santiago-Raber, M.-L., Walker, P.R., and Derouazi, M. (2019). Targeting self- and neoepitopes with a modular self-adjuvanting cancer vaccine. JCI Insight, 4. · DOI
  65. Ruseska, 2020, Internalization mechanisms of cell-penetrating peptides, Beilstein J. Nanotechnol., 11, 101, 10.3762/bjnano.11.10 · DOI
  66. Madani, 2011, Mechanisms of Cellular Uptake of Cell-Penetrating Peptides, J. Biophys., 2011, 1, 10.1155/2011/414729 · DOI
  67. Lim, 2016, Use of Cell-Penetrating Peptides in Dendritic Cell-Based Vaccination, Immune Netw., 16, 33, 10.4110/in.2016.16.1.33 · DOI
  68. Grau, 2018, Mechanistic insights into the efficacy of cell penetrating peptide-based cancer vaccines, Cell. Mol. Life Sci., 75, 2887, 10.1007/s00018-018-2785-0 · DOI
  69. Pouniotis, 2016, Vaccine delivery by penetratin: Mechanism of antigen presentation by dendritic cells, Immunol. Res., 64, 887, 10.1007/s12026-016-8799-5 · DOI
  70. Kopetz, 2021, SO-11 KISIMA-01 trial: Safety, tolerability and immunogenicity of ATP128 with or without ezabenlimab (BI 754091) in patients with stage IV colorectal cancer—Preliminary results from a phase 1b study, Ann. Oncol., 32, S206, 10.1016/j.annonc.2021.05.035 · DOI
  71. Linnemann, 2014, High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma, Nat. Med., 21, 81, 10.1038/nm.3773 · DOI
  72. Sahin, 2018, Personalized vaccines for cancer immunotherapy, Science, 359, 1355, 10.1126/science.aar7112 · DOI
  73. Matijass, 2021, Cell-penetrating peptides as part of therapeutics used in cancer research, Med. Drug Discov., 10, 100092, 10.1016/j.medidd.2021.100092 · DOI
  74. Kardani, K., and Bolhassani, A. (2021). Exploring novel and potent cell penetrating peptides in the proteome of SARS-COV-2 using bioinformatics approaches. PLoS ONE, 16. · DOI
  75. Zhang, 2019, Advances in mRNA Vaccines for Infectious Diseases, Front. Immunol., 10, 594, 10.3389/fimmu.2019.00594 · DOI

Metadata

Authors
Wylie, B., Ong, F., Belhoul-Fakir, H., Priebatsch, K., Bogdawa, H., Stirnweiss, A., Watt, P., Cunningham, P., Stone, S. R., & Waithman, J.
Affiliations
  • The Kids Research Institute Australia (AU)
  • PYC Therapeutics (Australia) (AU)
  • School of Public Health, Faculty of Health Sciences, Curtin University, Bentley, WA 6102, Australia
  • Exopharm, Melbourne, VIC 3000, Australia
  • Biocurate, Parkville, VIC 3052, Australia
  • Avicena, West Perth, WA 6005, Australia
  • The University of Western Australia (AU)
Corresponding author
  • Stone, Shane R.
  • Waithman, Jason
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2021-12-08
Volume
13
Issue
24
Pages
6189
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers13246189
PMC
PMC8699136
OpenAlex
W4200199869
Cited by
16
References
2
Citations by year
2026: 1 · 2025: 4 · 2023: 9 · 2022: 2
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UWA Profiles and Research Repository (University of Western Australia) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Cancer Council Western Australia (N/A)
  • Brady Cancer Support Foundation (N/A)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
cross-presentation, dendritic cells, peptide-based cancer vaccines, XCR1, XCL1, cell-penetrating peptides, endosomal escape, MHC class I antigen presentation, murine melanoma, B16 melanoma, antitumor immunity, prime-boost vaccination, antigen-specific T cells

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CoChat. (2026). Citation check: Targeting Cross-Presentation as a Route to Improve the Efficiency of Peptide-Based Cancer Vaccines. https://app.cochat.ai/papers/10.3390/cancers13246189
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Wylie, B., Ong, F., Belhoul-Fakir, H., Priebatsch, K., Bogdawa, H., Stirnweiss, A., Watt, P., Cunningham, P., Stone, S. R., & Waithman, J. (2021). Targeting Cross-Presentation as a Route to Improve the Efficiency of Peptide-Based Cancer Vaccines. Cancers. https://doi.org/10.3390/cancers13246189