2. Academic Validation
  3. LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion

LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion

  • J Nanobiotechnology. 2023 Sep 8;21(1):324. doi: 10.1186/s12951-023-02069-w.
Yu Xiang # 1,  Miaomiao Tian # 2,  Juan Huang # 3,  Yueyi Li 1,  Guangqi Li 1,  Xue Li 4,  Zedong Jiang 1,  Xiangrong Song 5,  Xuelei Ma 6 7
Affiliations

Affiliations

  • 1 Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 2 Department of Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 3 Department of Hematology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • 4 Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 5 Department of Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. songxr@scu.edu.cn.
  • 6 Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. drmaxuelei@gmail.com.
  • 7 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. drmaxuelei@gmail.com.
  • # Contributed equally.
PMID: 37679769 DOI: 10.1186/s12951-023-02069-w
Abstract

Background: Targeting EBV-proteins with mRNA vaccines is a promising way to treat EBV-related tumors like nasopharyngeal carcinoma (NPC). We assume that it may sensitize tumors to Immune Checkpoint inhibitors.

Results: We developed an LMP2-mRNA lipid nanoparticle (C2@mLMP2) that can be delivered to tumor-draining lymph nodes. C2@mLMP2 exhibited high transfection efficiency and lysosomal escape ability and induced an increased proportion of CD8 + central memory T cells and CD8 + effective memory T cells in the spleen of the mice model. A strong synergistic anti-tumor effect of C2@mLMP2 in combination with αPD-1 was observed in tumor-bearing mice. The mechanism was identified to be associated with a reverse of CD8 + T cell exhaustion in the tumor microenvironment. The pathological analysis further proved the safety of the vaccine and the combined therapy.

Conclusions: This is the first study proving the synergistic effect of the EBV-mRNA vaccine and PD-1 inhibitors for EBV-related tumors. This study provides theoretical evidence for further clinical trials that may expand the application scenario and efficacy of immunotherapy in NPC.

Keywords

Combined therapy; EBV; Immunotherapy; Lymph node targeting; Nasopharyngeal carcinoma; PD-1; mRNA vaccine.

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