An mRNA vaccine elicits STING-dependent antitumor immune responses

Zhe Chen; Chaoyang Meng; Junhua Mai; Yongbin Liu; Hangwen Li; Haifa Shen

doi:10.1016/j.apsb.2022.11.013

An mRNA vaccine elicits STING-dependent antitumor immune responses

Zhe Chen, Chaoyang Meng, Junhua Mai, Yongbin Liu, Hangwen Li, Haifa Shen

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

7 Scopus citations

Abstract

Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment, yet their mechanism of action and individual components contributing to such actions remain to be delineated. Here, we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8⁺ T cell responses and mediating anti-tumor immunity. Mechanistically, both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells. Stimulation of interferon-β expression is exclusively dependent on STING, and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene. Thus, the mRNA vaccine elicits STING-dependent antitumor immunity.

Original language	English (US)
Pages (from-to)	1274-1286
Number of pages	13
Journal	Acta Pharmaceutica Sinica B
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.apsb.2022.11.013
State	Published - Mar 2023

Keywords

Cancer
Dendritic cells
EDOPC
Immunotherapy
MAVS
STING
Vaccine
mRNA

ASJC Scopus subject areas

Pharmacology, Toxicology and Pharmaceutics(all)

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10.1016/j.apsb.2022.11.013

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title = "An mRNA vaccine elicits STING-dependent antitumor immune responses",

abstract = "Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment, yet their mechanism of action and individual components contributing to such actions remain to be delineated. Here, we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+ T cell responses and mediating anti-tumor immunity. Mechanistically, both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells. Stimulation of interferon-β expression is exclusively dependent on STING, and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene. Thus, the mRNA vaccine elicits STING-dependent antitumor immunity.",

keywords = "Cancer, Dendritic cells, EDOPC, Immunotherapy, MAVS, STING, Vaccine, mRNA",

author = "Zhe Chen and Chaoyang Meng and Junhua Mai and Yongbin Liu and Hangwen Li and Haifa Shen",

note = "Funding Information: This work was partially supported with a sponsored research grant from Stemirna Therapeutics , China, and from internal funding sources in Houston Methodist Research Institute , USA. Publisher Copyright: {\textcopyright} 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences",

year = "2023",

month = mar,

doi = "10.1016/j.apsb.2022.11.013",

language = "English (US)",

volume = "13",

pages = "1274--1286",

journal = "Acta Pharmaceutica Sinica B",

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publisher = "Elsevier BV",

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TY - JOUR

T1 - An mRNA vaccine elicits STING-dependent antitumor immune responses

AU - Chen, Zhe

AU - Meng, Chaoyang

AU - Mai, Junhua

AU - Liu, Yongbin

AU - Li, Hangwen

AU - Shen, Haifa

N1 - Funding Information: This work was partially supported with a sponsored research grant from Stemirna Therapeutics , China, and from internal funding sources in Houston Methodist Research Institute , USA. Publisher Copyright: © 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences

PY - 2023/3

Y1 - 2023/3

N2 - Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment, yet their mechanism of action and individual components contributing to such actions remain to be delineated. Here, we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+ T cell responses and mediating anti-tumor immunity. Mechanistically, both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells. Stimulation of interferon-β expression is exclusively dependent on STING, and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene. Thus, the mRNA vaccine elicits STING-dependent antitumor immunity.

AB - Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment, yet their mechanism of action and individual components contributing to such actions remain to be delineated. Here, we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+ T cell responses and mediating anti-tumor immunity. Mechanistically, both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells. Stimulation of interferon-β expression is exclusively dependent on STING, and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene. Thus, the mRNA vaccine elicits STING-dependent antitumor immunity.

KW - Cancer

KW - Dendritic cells

KW - EDOPC

KW - Immunotherapy

KW - MAVS

KW - STING

KW - Vaccine

KW - mRNA

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U2 - 10.1016/j.apsb.2022.11.013

DO - 10.1016/j.apsb.2022.11.013

M3 - Article

AN - SCOPUS:85148745580

SN - 2211-3835

VL - 13

SP - 1274

EP - 1286

JO - Acta Pharmaceutica Sinica B

JF - Acta Pharmaceutica Sinica B

IS - 3

ER -

An mRNA vaccine elicits STING-dependent antitumor immune responses

Abstract

Keywords

ASJC Scopus subject areas

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