Intravenous nanoparticle vaccination generates stem-like TCF1.sup.+ neoantigen-specific CD8.sup.+ T cells

Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoan...

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Bibliographic Details
Published inNature immunology Vol. 22; no. 1; pp. 41 - 52
Main Authors Baharom, Faezzah, Ramirez-Valdez, Ramiro A, Tobin, Kennedy K. S, Yamane, Hidehiro, Dutertre, Charles-Antoine, Khalilnezhad, Ahad, Reynoso, Glennys V
Format Journal Article
LanguageEnglish
Published Nature Publishing Group 01.01.2021
Subjects
Cancer
Cancer vaccines
Health aspects
Immune response
Observations
Oncology, Experimental
T cells
Testing
United States
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Summary:Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8.sup.+ T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1.sup.+PD-1.sup.+CD8.sup.+ T cells as compared to subcutaneous immunization (SNP-SC). Single-cell RNA sequencing showed that SNP-IV induced stem-like genes (Tcf7, Slamf6, Xcl1) whereas SNP-SC enriched for effector genes (Gzmb, Klrg1, Cx3cr1). Stem-like cells generated by SNP-IV proliferated and differentiated into effector cells upon checkpoint blockade, leading to superior antitumor response as compared to SNP-SC in a therapeutic model. The duration of antigen presentation by dendritic cells controlled the magnitude and quality of CD8.sup.+ T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8.sup.+ T cells.
ISSN:1529-2908
1529-2916
DOI:10.1038/s41590-020-00810-3