ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1633345
Bacterial outer membrane vesicles OMV-LL for delivery of neoantigen mRNA to induce anti-HCC therapy
Provisionally accepted
- 1Fujian Medical University, Fuzhou, China
- 2Fujian Medical University Union Hospital, Fuzhou, China
- 3Fujian Cancer Hospital, Fuzhou, China
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Hepatocellular carcinoma (HCC) represents a significant health challenge, with immunotherapy serving as a crucial component of its complex treatment regimen. This study investigates the use of TP53Y220C as a preferred antigen to induce cytotoxic T lymphocytes (CTLs) for cytotoxic effects against HCC. The TP53Y220C mRNA (mTP53Y220C) was synthesized through an in vitro transcription method and subsequently introduced into dendritic cells (DCs) using bacterial outer membrane vesicles expressing L7Ae and Listeria monocytogenes lysin O (OMV-LL), electroporation, and lipid nanoparticles, respectively. We assessed the therapeutic efficacy of CTLs, activated by mTP53Y220C-loaded DCs, in a murine model of HCC. Results demonstrate that CTLs, activated by DCs loaded with mTP53Y220C via OMV-LL or electroporation, effectively initiated immune responses against HCC. While OMV-LL were less efficient than electroporation in mRNA delivery, they induced a significant pro-inflammatory response and activated the innate immune system. This study highlights OMV-LL as an innovative mRNA delivery approach to DCs for CTLs activation and demonstrates their potential in CTLs-based therapy for HCC.
Keywords: mRNA, TP53, cytotoxic T lymphocytes, outer-membrane vesicles, Hepatocellular Carcinoma
Received: 22 May 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Cheng, Wu, Zhu, Lin, Liu, Chen and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yunbin Ye, Fujian Cancer Hospital, Fuzhou, China
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