Work

Membrane-IL12 adjuvant mRNA vaccine polarizes pre-effector T cells for optimized tumor control

Year: 2025

Type: article

Abstract: Conventional mRNA cancer vaccines can expand the quantity of tumor-specific CD8 T cells, but their effector function might be compromised. Specific cytokine signaling may enhance T cell differentiation for better tumor killing. We screened various cytokines and identified IL-12 as a potent adjuvant for mRNA vaccines, though with significant systemic toxicity. To balance efficacy and toxicity, we developed a membrane-tethered IL-12 (mtIL12) adjuvant mRNA vaccine. This design restricts mtIL12 expression to the surface of antigen-presenting cells, thereby selectively activating antigen-specific T cells without affecting bystander T or NK cells. mtIL12 adjuvant mRNA vaccination induced a unique pre-effector T cell subset that gives rise to highly responsive effector T cells, resulting in superior anti-tumor activity. Moreover, this approach overcame immune checkpoint therapy resistance and prevented cancer metastasis. Our study highlights that next-generation mRNA vaccines encoding membrane-tethered cytokine adjuvants can generate potent effector T cells, offering effective tumor control with reduced toxicity.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20241454

Authors: Kun Peng, Xiaoxue Zhao, Hongjian Li, Yang-Xin Fu, Yong Liang

Institutions: Changping Laboratory, Tsinghua University, State Key Laboratory of Molecular Oncology

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, National Outstanding Youth Science Fund Project of National Natural Science Foundation of China