Intravenous heterologous prime-boost vaccination activates innate and adaptive immunity to promote tumor regression

Ramiro A. Ramirez-Valdez, Faezzah Baharom, Ahad Khalilnezhad, Sloane C. Fussell, Dalton J. Hermans, Alexander M. Schrager, Kennedy K.S. Tobin, Geoffrey M. Lynn, Shabnam Khalilnezhad, Florent Ginhoux, Benoit J. Van den Eynde, Carol Sze Ki Leung, Andrew S. Ishizuka, Robert A. Seder

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    11 Citations (Scopus)

    Résumé

    Therapeutic neoantigen cancer vaccines have limited clinical efficacy to date. Here, we identify a heterologous prime-boost vaccination strategy using a self-assembling peptide nanoparticle TLR-7/8 agonist (SNP) vaccine prime and a chimp adenovirus (ChAdOx1) vaccine boost that elicits potent CD8 T cells and tumor regression. ChAdOx1 administered intravenously (i.v.) had 4-fold higher antigen-specific CD8 T cell responses than mice boosted by the intramuscular (i.m.) route. In the therapeutic MC38 tumor model, i.v. heterologous prime-boost vaccination enhances regression compared with ChAdOx1 alone. Remarkably, i.v. boosting with a ChAdOx1 vector encoding an irrelevant antigen also mediates tumor regression, which is dependent on type I IFN signaling. Single-cell RNA sequencing of the tumor myeloid compartment shows that i.v. ChAdOx1 reduces the frequency of immunosuppressive Chil3 monocytes and activates cross-presenting type 1 conventional dendritic cells (cDC1s). The dual effect of i.v. ChAdOx1 vaccination enhancing CD8 T cells and modulating the TME represents a translatable paradigm for enhancing anti-tumor immunity in humans.

    langue originaleAnglais
    Numéro d'article112599
    journalCell Reports
    Volume42
    Numéro de publication6
    Les DOIs
    étatPublié - 27 juin 2023

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