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Repurposing the yellow fever vaccine for intratumoral immunotherapy

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Aznar, Maria Angela, Molina, Carmen, Teijeira, Alvaro, Rodriguez, Inmaculada, Azpilikueta, Arantza, Garasa, Saray, Sanchez‐Paulete, Alfonso R, Cordeiro, Luna, Etxeberria, Iñaki, Alvarez, Maite, Rius‐Rocabert, Sergio, Nistal‐Villan, Estanislao, Berraondo, Pedro, Melero, Ignacio·2020·EMBO Molecular Medicine
DOI 10.15252/emmm.201910375PMC PMC6949490
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Abstract

Live 17D is widely used as a prophylactic vaccine strain for yellow fever virus that induces potent neutralizing humoral and cellular immunity against the wild‐type pathogen. 17D replicates and kills mouse and human tumor cell lines but not non‐transformed human cells. Intratumoral injections with viable 17D markedly delay transplanted tumor progression in a CD8 T‐cell‐dependent manner. In mice bearing bilateral tumors in which only one is intratumorally injected, contralateral therapeutic effects are observed consistent with more prominent CD8 T‐cell infiltrates and a treatment‐related reduction of Tregs. Additive efficacy effects were observed upon co‐treatment with intratumoral 17D and systemic anti‐CD137 and anti‐PD‐1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized with 17D, intratumoral 17D treatment achieved better local and distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8 T‐cell infiltration in the treated tumor. The repurposed use of a GMP‐grade vaccine to be given via the intratumoral route in prevaccinated patients constitutes a clinically feasible and safe immunotherapy approach.

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  • Intratumoral delivery of the prophylactic yellow fever vaccine (live 17D) into mice stimulated immune-mediated antitumor effects including orchestration of cytotoxic T lymphocytes and suppression of Tregs.

    “Another study reported that intratumoral delivery of the prophylactic yellow fever vaccine (live 17D) into mice stimulated immune-mediated antitumor effects including the orchestration of cytotoxic T lymphocytes and suppression of Tregs.264”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [264]

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Metadata

Authors
Aznar, M. A., Molina, C., Teijeira, A., Rodriguez, I., Azpilikueta, A., Garasa, S., Sanchez‐Paulete, A. R., Cordeiro, L., Etxeberria, I., Alvarez, M., Rius‐Rocabert, S., Nistal‐Villan, E., Berraondo, P., & Melero, I.
Affiliations
  • Centro de Investigación Médica Aplicada (ES)
  • Navarre Institute of Health Research (ES)
  • Universidad San Pablo CEU (ES)
Corresponding author
  • Aznar, Maria Angela
  • Melero, Ignacio
ORCID
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2019-11-19
Volume
12
Issue
1
Pages
e10375-e10375
ISSN
  • 1757-4676 (ISSN-L)
  • 1757-4684
DOI
10.15252/emmm.201910375
PMC
PMC6949490
OpenAlex
W2991001158
Cited by
44
References
62
Citations by year
2026: 2 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 2
FWCI
2.30
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • CEU Repositorio Institucional (Fundación Universitaria San Pablo CEU) (submittedVersion, cc-by-nc-nd)
Funders
  • Spanish Ministry of Economy and Competitiveness MEC (SAF2014‐52361‐R, SAF2017–83267‐C2–1‐R)
  • Fundación Científica Asociación Española Contra el Cáncer
  • Cancer Research Institute
  • Fundación BBVA
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
Keywords
intratumoral immunotherapy, cancer immunotherapy, tumor cell killing, CD8+ T cells, regulatory T cells, anti-PD-1, anti-CD137, tumor-infiltrating T cells, vaccine repurposing, antitumor immunity
MeSH terms
Animals, Female, Humans, Immunotherapy, Mice, Inbred C57BL, Neoplasms, CD8-Positive T-Lymphocytes, Yellow Fever Vaccine, Mice, Drug Repositioning

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