Repurposing the yellow fever vaccine for intratumoral immunotherapy. Issue 1 (19th November 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: EMBO molecular medicine. Volume 12:Issue 1(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-11-19
• Subjects: 17D -- cancer immunotherapy -- intratumoral administration -- virotherapy -- yellow fever vaccine; Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.201910375
• Languages: English
• ISSNs: 1757-4676

Abstract

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. Synopsis: The attenuated vaccine for yellow fever virus exerts antitumor effects when intratumorally injected which are mediated by immune responses and enhanced in pre‐vaccinated mice. Repeated intratumoral injection of 17D virus stimulates antitumor responses and delays tumor growth in transplantable tumor models through a mechanism dependent on CD8 + T cells that requires cDC1 dendritic cells and functional IFNα signaling. 17D intratumoral injection modifies immune infiltration in injected and distant tumors as well as in tumor draining lymph nodes. Preimmunization of mice with 17D vaccine potentiates the antitumor effects of intratumoral 17D and this beneficial effect is transferred along with CD8 T cells. Abstract : The attenuated vaccine for yellow fever virus exerts antitumor effects when intratumorally injected which are mediated by immune responses and enhanced in pre‐vaccinated mice.