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Breaking the Tumor Chronic Inflammation Balance with a Programmable Release and Multi-Stimulation Engineering
Xiuqi Liang1, Xinchao Li1, Rui Wu1
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Summary
This study introduces PHOENIX, a novel hydrogel scaffold that releases immunotherapy drugs in response to tumor conditions. PHOENIX effectively combats cold tumors by reprogramming the immune microenvironment and enhancing anti-cancer immune responses.
Area of Science:
- Biomaterials Science
- Immunology
- Cancer Therapy
Background:
- Chronic inflammation in cold tumors hinders immunotherapy efficacy.
- Tumor microenvironments often suppress anti-cancer immune responses.
Purpose of the Study:
- To develop a programmable hydrogel scaffold (PHOENIX) to overcome chronic inflammation in cold tumors.
- To engineer a multi-stimuli responsive system for controlled drug release to enhance immunotherapy.
Main Methods:
- PHOENIX scaffold designed for programmable release of resiquimod and anti-OX40 under reactive oxygen species (ROS).
- Sequential drug release to modulate immune cells: resiquimod for antigen-presenting cell maturation and myeloid-derived suppressor cell transformation, followed by anti-OX40 for T-cell activation.
Main Results:
- PHOENIX effectively broke chronic inflammation and induced potent anti-tumor immunity in mouse models.
- Significant tumor growth inhibition (80% in triple-negative breast cancer, 60% in metastasis).
- 100% protection against tumor rechallenge in TNBC models, indicating long-term immune memory.
Conclusions:
- PHOENIX is a potent therapeutic scaffold for improving immunotherapy in cold tumors.
- This approach offers a generalizable and facile regimen for enhancing cancer immunotherapy.
- Demonstrated efficacy in triple-negative breast cancer, colorectal cancer, and melanoma models.
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