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

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. Mulè; 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

doi:10.1038/s41590-020-00810-3

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

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. Mulè, 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

Research output: Contribution to journal › Article › peer-review

120 Citations (Scopus)

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 TCF1⁺PD-1⁺CD8⁺ 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.

Original language	English
Pages (from-to)	41-52
Number of pages	12
Journal	Nature Immunology
Volume	22
Issue number	1
DOIs	https://doi.org/10.1038/s41590-020-00810-3
Publication status	Published - 1 Jan 2021
Externally published	Yes

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Baharom, F., Ramirez-Valdez, R. A., Tobin, K. K. S., Yamane, H., Dutertre, C. A., Khalilnezhad, A., Reynoso, G. V., Coble, V. L., Lynn, G. M., Mulè, M. P., Martins, A. J., Finnigan, J. P., Zhang, X. M., Hamerman, J. A., Bhardwaj, N., Tsang, J. S., Hickman, H. D., Ginhoux, F., Ishizuka, A. S., & Seder, R. A. (2021). Intravenous nanoparticle vaccination generates stem-like TCF1⁺ neoantigen-specific CD8⁺ T cells. Nature Immunology, 22(1), 41-52. https://doi.org/10.1038/s41590-020-00810-3

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title = "Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells",

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 TCF1+PD-1+CD8+ 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.",

author = "Faezzah Baharom and Ramirez-Valdez, {Ramiro A.} and Tobin, {Kennedy K.S.} and Hidehiro Yamane and Dutertre, {Charles Antoine} and Ahad Khalilnezhad and Reynoso, {Glennys V.} and Coble, {Vincent L.} and Lynn, {Geoffrey M.} and Mul{\`e}, {Matthew P.} and Martins, {Andrew J.} and Finnigan, {John P.} and Zhang, {Xiao Meng} and Hamerman, {Jessica A.} and Nina Bhardwaj and Tsang, {John S.} and Hickman, {Heather D.} and Florent Ginhoux and Ishizuka, {Andrew S.} and Seder, {Robert A.}",

note = "Publisher Copyright: {\textcopyright} 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",

year = "2021",

month = jan,

day = "1",

doi = "10.1038/s41590-020-00810-3",

language = "English",

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journal = "Nature Immunology",

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Baharom, F, Ramirez-Valdez, RA, Tobin, KKS, Yamane, H, Dutertre, CA, Khalilnezhad, A, Reynoso, GV, Coble, VL, Lynn, GM, Mulè, MP, Martins, AJ, Finnigan, JP, Zhang, XM, Hamerman, JA, Bhardwaj, N, Tsang, JS, Hickman, HD, Ginhoux, F, Ishizuka, AS & Seder, RA 2021, 'Intravenous nanoparticle vaccination generates stem-like TCF1⁺ neoantigen-specific CD8⁺ T cells', Nature Immunology, vol. 22, no. 1, pp. 41-52. https://doi.org/10.1038/s41590-020-00810-3

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T1 - Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells

AU - Baharom, Faezzah

AU - Ramirez-Valdez, Ramiro A.

AU - Tobin, Kennedy K.S.

AU - Yamane, Hidehiro

AU - Dutertre, Charles Antoine

AU - Khalilnezhad, Ahad

AU - Reynoso, Glennys V.

AU - Coble, Vincent L.

AU - Lynn, Geoffrey M.

AU - Mulè, Matthew P.

AU - Martins, Andrew J.

AU - Finnigan, John P.

AU - Zhang, Xiao Meng

AU - Hamerman, Jessica A.

AU - Bhardwaj, Nina

AU - Tsang, John S.

AU - Hickman, Heather D.

AU - Ginhoux, Florent

AU - Ishizuka, Andrew S.

AU - Seder, Robert A.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - 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 TCF1+PD-1+CD8+ 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.

AB - 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 TCF1+PD-1+CD8+ 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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U2 - 10.1038/s41590-020-00810-3

DO - 10.1038/s41590-020-00810-3

M3 - Article

C2 - 33139915

AN - SCOPUS:85094941727

SN - 1529-2908

VL - 22

SP - 41

EP - 52

JO - Nature Immunology

JF - Nature Immunology

IS - 1

ER -

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

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