Synergically enhanced anti-tumor immunity of in vivo panCAR by circRNA vaccine boosting
Chimeric antigen receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies, but it still faces challenges, including high costs, a time-consuming manufacturing process, and the necessity of lymphodepletion. Here, we generate circular RNAs (circRNAs) encoding CAR proteins, referred to as circRNA<sup>CAR</sup>, which mediates remarkable tumor killing in human primary T cells. We demonstrate that circRNA<sup>CAR</sup>, delivered with immunocyte-tropic lipid nanoparticles (LNPs), can form in vivo panCAR cells (CAR-T, CAR-natural killer [NK], and CAR-macrophage), significantly inhibit tumor growth, and reshape the tumor microenvironment in mice. Importantly, combining in vivo panCAR with circRNA-based vaccines encoding the corresponding HER2 antigens exhibits synergistically enhanced anti-tumor immunity. Notably, circRNA<sup>CAR</sup> can in return boost the level of vaccination-elicited HER2-specific antibodies, mediating effective killing of tumor cells by macrophages. In combination with vaccination, in vivo panCAR demonstrates a synergistic enhancement of anti-tumor immunity across various mouse models, thereby establishing a framework for the synergistic in vivo panCAR-VAC immunotherapy.
Authors
- H. Kou (ORCID: https://orcid.org/0000-0003-4927-243X)
- Yichi Xu (ORCID: https://orcid.org/0000-0002-8163-3920)
- Liang Qu (ORCID: https://orcid.org/0000-0002-4063-2972)
- Xinyuan Liao
- Fei Gao (ORCID: https://orcid.org/0000-0002-4086-2575)
- Jinzhong Lin (ORCID: https://orcid.org/0000-0001-5666-8526)
- Min Qiu (ORCID: https://orcid.org/0000-0002-7373-2355)
- Jie Yin (ORCID: https://orcid.org/0000-0002-5419-6315)
- Jing Li (ORCID: https://orcid.org/0000-0002-3681-4095)
- Xinyang Li (ORCID: https://orcid.org/0000-0003-1731-0155)
- Yanyan Wang (ORCID: https://orcid.org/0000-0002-0752-3256)
- Chenchen Zhang (ORCID: https://orcid.org/0000-0001-8563-5002)
- Xinyue Wang (ORCID: https://orcid.org/0000-0001-7320-4926)
- Dan Luo (ORCID: https://orcid.org/0000-0002-7555-0045)
- Liangru Lin
- Chengzhi Zhao (ORCID: https://orcid.org/0000-0002-4880-8223)
- Qian Pan (ORCID: https://orcid.org/0000-0002-5706-9119)
- Qi Yin (ORCID: https://orcid.org/0000-0002-6382-5005)
Institutions
- Fudan University (CN)
- Southern University of Science and Technology (CN)
- Beijing Institute of Nanoenergy and Nanosystems (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102250
- Citations
- 16
- Primary Topic
- Circular RNAs in diseases
- Type
- article
- Field-Weighted Citation Impact
- 12.90
Funders
- Shanghai Municipal Health Commission
- National Natural Science Foundation of China
- Fudan University
- Shanghai Municipal Education Commission
- Science and Technology Commission of Shanghai Municipality
- Shanghai Rising-Star Program
- Shanghai Medical College, Fudan University