Citation: Peng Gao, Yuanyuan Chen, Qianlin He, Xue Liu, Echuan Tan, Zhiqiang Yu, Hui Wang. Highly efficient adoptive cell therapy of metastatic triple negative breast cancer with bioactive covalent organic framework-engineered macrophages[J]. Chinese Chemical Letters, ;2025, 36(8): 110585. doi: 10.1016/j.cclet.2024.110585 shu

Highly efficient adoptive cell therapy of metastatic triple negative breast cancer with bioactive covalent organic framework-engineered macrophages

Peng Gao ^{a, 1} ,
Yuanyuan Chen ^{b, 1} ,
Qianlin He ^a ,
Xue Liu ^b ,
Echuan Tan ^c ,
Zhiqiang Yu ^{b, *,} ,
Hui Wang ^{a, *,}

a.
South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, China
b.
Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523018, China
c.
School of Life Sciences, East China Normal University, Shanghai 200241, China

yuzq@smu.edu.cn

wangh@scut.edu.cn

Received Date: 17 July 2024
Revised Date: 24 October 2024
Accepted Date: 27 October 2024
Available Online: 29 October 2024

Figures(5)

Triple-negative breast cancer (TNBC) is one of the most lethal diseases and lack of feasible therapeutic methods. Herein, we developed a bioactive covalent organic framework (COF) for adoptive cell therapy (ACT) of TNBC. In our design, Mn²⁺ functionalized COF was employed as a bioactive CpG carrier, which could simultaneously engineer and polarize macrophages to the antitumor phenotype, via the synergistic interaction of CpG and Mn²⁺. In the in vitro experiments, the engineered macrophages were found to secret high levels of antitumor cytokines for efficient TNBC cell inhibition. In the in vivo antitumor model, bioactive COF-engineered macrophages were found to relieve the hypoxia tumor microenvironment, enabling prevention of immune cell depletion during ACT. Thus, we realized efficient TNBC therapy and metastasis inhibition with the engineered macrophages in a long-term therapy model. This work provides a promising strategy for metastatic TNBC treatment and highlights the importance of bioactive COF in biomedicine.
- Covalent organic framework,
- Adoptive cell therapy,
- Triple negative breast cancer,
- Hypoxia tumor,
- Immunosuppressive microenvironment
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沈阳化工大学材料科学与工程学院沈阳 110142