An mRNA Tumor Nanovaccine Expressing Tumor Antigen Fused With Angiotensin II Facilitates Type 1 Conventional Dendritic Cell-Mediated Anti-Tumor Immunity

  • Small. 2026 Jun;22(32):e13524. doi: 10.1002/smll.202513524.
Chunyuan Xie  1 ,  Hui Guo  1  2 ,  Chunlei Dai  1 ,  Liying Wang  3 ,  Ruhui Yao  1 ,  Lei Cui  1 ,  Xinru You  4 ,  Zining Wang  1 ,  Hongxia Zhang  5  6 ,  Huanling Zhang  7 ,  Lin Li  1 ,  Tiantian Wang  1 ,  Zixuan Guo  1 ,  Yanxun Lin  1 ,  Jiahong Yi  1 ,  Jiaxin Wu  1 ,  Ju Xue  1 ,  Huan Jin  1 ,  Yue Zhao  1 ,  Zhiming Wu  1  8 ,  Jun Wu  3 ,  Xiaojun Xia  1  9
Affiliations
  • 1. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 2. Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Pathology and Institute of Molecular Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 3. Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, China.
  • 4. Center For Nanomedicine and Department of Anesthesiology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • 5. Department of Pathology, School of Basic Medical Sciences, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 6. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
  • 7. Guangzhou National Laboratory, Guangzhou, China.
  • 8. Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 9. Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China.
PMID: 42043950 DOI: 10.1002/smll.202513524
Abstract

mRNA-based tumor vaccines have shown great potential as a promising immunotherapeutic approach with encouraging preclinical and clinical results. However, how to enhance the antigen presentation efficiency of mRNA-encoded tumor antigens and the intensity of vaccine-induced CD8+ T cell response remains a great challenge. In this study, an antigen-angiotensin II (ANG II) fusion mRNA nanovaccine that can enhance the immunogenicity of tumor antigens to promote CD8+ T cell immunity for effective tumor inhibition is developed. Furthermore, this mRNA nanovaccine is delivered by lipid nanoparticles (LNPs) composed of cationic lipid-like material C1 and L-phenylalanine-based poly (ester amide) 8p4, which promotes the maturation of dendritic cells (DCs) and increases the type 1 conventional DC (cDC1) subpopulation, together enhancing the antigen presentation function of DCs for eliciting potent antigen-specific CD8+ T cell response. Vaccination with the antigen-ANG II mRNA nanovaccine expressing different tumor antigens effectively inhibited tumor growth on multiple mouse tumor models, which was greatly compromised in the cDC1-deficient Batf3-/- mice. Overall, this work provides an antigen-ANG II fusion mRNA tumor nanovaccine platform with remarkable antitumor efficacy via triggering cDC1-mediated CD8+ T cell response.

Keywords
ANG II; adjuvant; cDC1; mRNA tumor nanovaccine.
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