The guided fire from within: intratumoral administration of mRNA-based vaccines to mobilize memory immunity and direct immune responses against pathogen to target solid tumors

被引：0

作者：

Li, Renhao ^{[1
,2
]}

Hu, Jing-Chu ^{[1
]}

Rong, Li ^{[1
]}

He, Yige ^{[1
]}

Wang, Xiaolei ^{[1
,3
]}

Lin, Xuansheng ^{[1
]}

Li, Wenjun ^{[1
]}

Wu, Yangfan ^{[1
,2
]}

Kuwentrai, Chaiyaporn ^{[1
]}

Su, Canhui ^{[1
]}

Yau, Thomas ^{[2
]}

Hung, Ivan Fan-Ngai ^{[2
]}

Gao, Xiang ^{[4
]}

Huang, Jian-Dong ^{[1
,3
,5
,6
,7
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Pokfulam, Hong Kong, Peoples R China

[2] Univ Hong Kong, Li Ka Shing Fac Med, Sch Clin Med, Dept Med, Hong Kong, Peoples R China

[3] Univ Hong Kong, Shenzhen Hosp, Dept Clin Oncol, Shenzhen Key Lab Canc Metastasis & Personalized Th, Shenzhen, Guangdong, Peoples R China

[4] PGR Solut Inc, Durham, NC 27703 USA

[5] Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Key Lab Quantitat Synthet Biol, Shenzhen, Peoples R China

[6] Sun Yat Sen Univ, Guangdong Hong Kong Joint Lab RNA Med, Guangzhou 510120, Peoples R China

[7] HKU SIRI, Mat Innovat Inst Life Sci & Energy MILES, Shenzhen, Guangdong, Peoples R China

来源：

CELL DISCOVERY | 2025年 / 10卷 / 01期

基金：

国家重点研发计划;

关键词：

CELLS; IMMUNOTHERAPY; SUPPRESSION; EXOSOMES; GENE;

D O I：

10.1038/s41421-024-00743-3

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We investigated a novel cancer immunotherapy strategy that effectively suppresses tumor growth in multiple solid tumor models and significantly extends the lifespan of tumor-bearing mice by introducing pathogen antigens into tumors via mRNA-lipid nanoparticles. The pre-existing immunity against the pathogen antigen can significantly enhance the efficacy of this approach. In mice previously immunized with BNT162b2, an mRNA-based COVID-19 vaccine encoding the spike protein of the SARS-CoV-2 virus, intratumoral injections of the same vaccine efficiently tagged the tumor cells with mRNA-expressed spike protein. This action rapidly mobilized the pre-existing memory immunity against SARS-CoV-2 to kill the cancer cells displaying the spike protein, while concurrently reprogramming the tumor microenvironment (TME) by attracting immune cells. The partial elimination of tumor cells in a normalized TME further triggered extensive tumor antigen-specific T cell responses through antigen spreading, eventually resulting in potent and systemic tumor-targeting immune responses. Moreover, combining BNT162b2 treatment with anti-PD-L1 therapy yielded a more substantial therapeutic impact, even in "cold tumor" types that are typically less responsive to treatment. Given that the majority of the global population has acquired memory immunity against various pathogens through infection or vaccination, we believe that, in addition to utilizing the widely held immune memory against SARS-CoV-2 via COVID-19 vaccine, mRNA vaccines against other pathogens, such as Hepatitis B Virus (HBV), Common Human Coronaviruses (HCoVs), and the influenza virus, could be rapidly transitioned into clinical use and holds great promise in treating different types of cancer. The extensive selection of pathogen antigens expands therapeutic opportunities and may also overcome potential drug resistance.

引用

页数：18