CD73-LNPs promote antitumor T-cell immunity via amplifying TLR3-mediated immunostimulatory dendritic cell activation
- 1Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University
- 2Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University
- 3Research and Development Center, Shenzhen MagicRNA Biotech
Abstract
Background mRNA vaccines have emerged as highly promising therapeutic agents in cancer immunotherapy. Nevertheless, the current limited immunogenicity of target antigens and the lack of a robust systemic immune response remain significant challenges for their effective application. This study aimed to evaluate the immunogenicity of the CD73 protein and elucidate the mechanisms by which a CD73 mRNA vaccine mediates antitumor immune effects in murine models. Methods CD73 mRNA was synthesized by in vitro transcription and formulated into lipid nanoparticles (CD73-LNPs) using a microfluidic device. The immunogenicity of CD73 was assessed using ELISPOT assays. The ability of CD73-LNPs to activate antitumor immune responses was evaluated by flow cytometry. Therapeutic efficacy was tested in murine models of melanoma, cervical cancer, ovarian cancer, and prostate cancer. Mechanistic insights were obtained through single-cell transcriptomics sequencing and bulk RNA transcriptomic analysis. Results The CD73 protein exhibited potent immunogenicity. In vitro, CD73-LNPs promoted the maturation and activation of primary dendritic cells. In vivo, CD73-LNPs induced humoral and cellular immune responses, increased the secretion of interferon-gamma and granzyme B, and effectively suppressed tumor growth across multiple tumor models. Mechanistically, CD73-LNPs activated dendritic cells through toll-like receptor 3 (TLR3) signaling, enhanced dendritic cell activation, and upregulated chemokine receptor expression on CD8+ T cells, thereby promoting CD8+ T cell infiltration into the tumor microenvironment. Safety evaluations revealed no toxic effects on vital organs. Conclusion CD73 mRNA vaccine safely and effectively induces antitumor immunity through TLR3-dependent mechanisms, highlighting their considerable potential for clinical translation. Graphical Abstract
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BibTeX
@article{xu2026cd73lnps,
title = {{CD73-LNPs promote antitumor T-cell immunity via amplifying TLR3-mediated immunostimulatory dendritic cell activation}},
author = {Yuandong Xu and Fei Cao and Haowei Qiu and Yi Zhang and Yiting Wang and Zhen Xu and Yunru He and Ze-Xiu Xiao and Gao-Feng Zha and Jun Pang},
journal = {Journal of Translational Medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08666-1},
url = {https://doi.org/10.1186/s12967-026-08666-1},
note = {CC BY},
}
RIS
TY - JOUR
TI - CD73-LNPs promote antitumor T-cell immunity via amplifying TLR3-mediated immunostimulatory dendritic cell activation
AU - Yuandong Xu
AU - Fei Cao
AU - Haowei Qiu
AU - Yi Zhang
AU - Yiting Wang
AU - Zhen Xu
AU - Yunru He
AU - Ze-Xiu Xiao
AU - Gao-Feng Zha
AU - Jun Pang
PY - 2026
DA - 2026/07/01
JO - Journal of Translational Medicine
DO - 10.1186/s12967-026-08666-1
UR - https://doi.org/10.1186/s12967-026-08666-1
AB - Background mRNA vaccines have emerged as highly promising therapeutic agents in cancer immunotherapy. Nevertheless, the current limited immunogenicity of target antigens and the lack of a robust systemic immune response remain significant challenges for their effective application. This study aimed to evaluate the immunogenicity of the CD73 protein and elucidate the mechanisms by which a CD73 mRNA vaccine mediates antitumor immune effects in murine models. Methods CD73 mRNA was synthesized by in vitro transcription and formulated into lipid nanoparticles (CD73-LNPs) using a microfluidic device. The immunogenicity of CD73 was assessed using ELISPOT assays. The ability of CD73-LNPs to activate antitumor immune responses was evaluated by flow cytometry. Therapeutic efficacy was tested in murine models of melanoma, cervical cancer, ovarian cancer, and prostate cancer. Mechanistic insights were obtained through single-cell transcriptomics sequencing and bulk RNA transcriptomic analysis. Results The CD73 protein exhibited potent immunogenicity. In vitro, CD73-LNPs promoted the maturation and activation of primary dendritic cells. In vivo, CD73-LNPs induced humoral and cellular immune responses, increased the secretion of interferon-gamma and granzyme B, and effectively suppressed tumor growth across multiple tumor models. Mechanistically, CD73-LNPs activated dendritic cells through toll-like receptor 3 (TLR3) signaling, enhanced dendritic cell activation, and upregulated chemokine receptor expression on CD8+ T cells, thereby promoting CD8+ T cell infiltration into the tumor microenvironment. Safety evaluations revealed no toxic effects on vital organs. Conclusion CD73 mRNA vaccine safely and effectively induces antitumor immunity through TLR3-dependent mechanisms, highlighting their considerable potential for clinical translation. Graphical Abstract
SN - 1479-5876
ER -