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ATP-Inducible Receptor Oligomerization Enables Fine-Tuning of T Cell Immunity
Jianjun He1, Haoxiang Li1, Fuling Liang1
1The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.
Angewandte Chemie (International Ed. in English)
|June 16, 2025
Summary
This study introduces an Adenosine Triphosphate (ATP)-Inducible Receptor Oligomerization (ATIRO) approach. ATIRO enhances anti-tumor immunity by activating T cells within the tumor microenvironment (TME), effectively suppressing tumor growth.
Area of Science:
- Immunology
- Biotechnology
- Cancer Research
Background:
- Receptor oligomerization is crucial for cellular signaling.
- Stimuli-responsive systems can reprogram cell signaling pathways.
- Tumor microenvironment (TME)-responsive systems offer novel cancer therapeutic strategies.
Purpose of the Study:
- To introduce an Adenosine Triphosphate (ATP)-inducible receptor oligomerization (ATIRO) approach.
- To enhance anti-tumor immunity by facilitating T cell engagement.
- To develop a TME-responsive system for targeted cancer therapy.
Main Methods:
- Developed an ATIRO system to cluster CD3 and CD8 on T cells.
- Engineered T cells to engage tumor markers via CD3.
- Utilized high ATP levels in the TME for in situ T cell activation.
Main Results:
- ATIRO successfully facilitated T cell clustering and tumor marker engagement.
- In vivo studies demonstrated effective suppression of tumor growth.
- The system showed specific activation of T cells within the TME.
Conclusions:
- ATIRO is a versatile strategy for in situ T cell immunity reconfiguration.
- This approach holds significant potential for advancing cancer therapeutic interventions.
- The TME-responsive system offers enhanced therapeutic effectiveness and safety.
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