Related Experiment Video
Updated: Feb 28, 2026
A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
An engineered linear cap-independent mRNA vaccine with intrinsic adjuvanticity induces potent anti-tumor immunity in
Hongwu Yu1,2, Yu Yang1,2, Peng Lin1,2
1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Abstract:
mRNA cancer vaccines demonstrate potential in clinical trials, but existing platforms struggle to boost antitumor efficacy without added cost or complexity. Here, we present a streamlined linear cap-independent mRNA (LciRNA) cancer vaccine platform, achieved by fusing a UPA protective sequence, composed of a viral exoribonuclease-resistant RNA (xrRNA) and a poly(A) binding protein (PABP) motif, to an optimized Enterovirus A internal ribosome entry site. UPA impedes exonuclease-mediated decay and recruits RNA-binding proteins to stabilize LciRNA, enabling stable in vivo expression without 5' capping or modifications. Moreover, LciRNA innately stimulates immune responses by engaging pattern-recognition receptors, promoting dendritic cell maturation, and upregulating proinflammatory signals. In murine melanoma and HPV-associated tumor models, this vaccine platform elicits strong systemic and intra-tumoral T cell responses, achieving superior tumor control, demonstrating how immune stimulation-translation synergy underpins its efficacy. Thus, we present a cost-effective platform with enhanced efficacy, and highlight coupled immune stimulation and translation as a paradigm for future mRNA cancer vaccines.
