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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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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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