Intravenous Nanoparticle Vaccination Generates Stem-like TCF1 Neoantigen-specific CD8 T Cells

Overview

Journal Nat Immunol

Date 2020 Nov 3

PMID 33139915

Citations 85

Authors

Faezzah Baharom

Ramiro A Ramirez-Valdez

Kennedy K S Tobin

Hidehiro Yamane

Charles-Antoine Dutertre

Ahad Khalilnezhad

Glennys V Reynoso

Vincent L Coble

Geoffrey M Lynn

Matthew P Mule

Andrew J Martins

John P Finnigan

Xiao Meng Zhang

Jessica A Hamerman

Nina Bhardwaj

John S Tsang

Heather D Hickman

Florent Ginhoux

Andrew S Ishizuka

Robert A Seder

Affiliations

Soon will be listed here.

Abstract

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 T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1PD-1CD8 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 T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8 T cells.

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