Repurposing the yellow fever vaccine for intratumoral immunotherapy.
17D
cancer immunotherapy
intratumoral administration
virotherapy
yellow fever vaccine
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
09 01 2020
09 01 2020
Historique:
received:
25
01
2019
revised:
22
10
2019
accepted:
24
10
2019
pubmed:
21
11
2019
medline:
28
7
2021
entrez:
21
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31746149
doi: 10.15252/emmm.201910375
pmc: PMC6949490
doi:
Substances chimiques
Yellow Fever Vaccine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e10375Subventions
Organisme : Spanish Ministry of Economy and Competitiveness MEC
ID : SAF2014-52361-R
Pays : International
Organisme : Spanish Ministry of Economy and Competitiveness MEC
ID : SAF2017-83267-C2-1-R
Pays : International
Organisme : Fundación Científica Asociación Española Contra el Cáncer (AECC)
Pays : International
Organisme : Cancer Research Institute (CRI)
Pays : International
Organisme : Fundación BBVA
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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