Citation: Honghao Sun, Huimin Zhao, Ronghui Yin, Chenxi Zhou, Ming Wu, Yueyang Deng, Zhanwei Zhou, Minjie Sun. Injectable hydrogel-based tumor vaccine with fibrotic tumor immune microenvironment remodeling to prevent breast cancer postoperative recurrence and metastases[J]. Chinese Chemical Letters, ;2025, 36(5): 110067. doi: 10.1016/j.cclet.2024.110067 shu

Injectable hydrogel-based tumor vaccine with fibrotic tumor immune microenvironment remodeling to prevent breast cancer postoperative recurrence and metastases

NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China

zwzhou@cpu.edu.cn

msun@cpu.edu.cn

Received Date: 30 March 2024
Revised Date: 27 May 2024
Accepted Date: 28 May 2024
Available Online: 29 May 2024

Figures(5)

Postoperative recurrence and metastasis are still the main challenges of cancer therapy. Tumor vaccines that induce potent and long-lasting immune activation have great potential for postoperative cancer therapy. However, the clinical effects of therapeutic tumor vaccines are unsatisfactory due to immune escape caused by the lack of immunogenicity after surgery and the local fibrosis barrier of the tumor which limits effector T cell infiltration. To overcome these challenges, we developed an injectable hydrogel-based tumor vaccine, RATG, which contains whole tumor cell lysates (TCL), Toll-like receptor (TLR) 7/8 agonist imiquimod (R837) and an antifibrotic drug ARV-825. TCL and R837 were loaded onto the hydrogel to achieve a powerful reservoir of antigens and adjuvants that induced potent and lasting immune activation. More importantly, ARV-825 could be slowly and sustainably released in the tumor resection cavity to downregulate α-smooth muscle actin (α-SMA) and collagen levels, disintegrate fibrosis barriers and promote T cell infiltration after immune activation to reduce immune escape. In addition, ARV-825 also directly acted on the remaining tumor cells to degrade bromodomain-containing protein 4 (BRD4) which is a critical epigenetic reader overexpressed in tumor cells, inhibiting tumor cell migration and invasion. Therefore, our injectable hydrogel created a powerful immune niche in postoperative tumor resection cavity, significantly enhancing the efficacy of tumor vaccines. Our strategy potently activates the immune system and disintegrates the fibrotic barrier of residual tumors with immune microenvironment remodeling in situ, showing anti-recurrence and anti-metastatic effects, and provides a new paradigm for postoperative treatment of tumors.
- Injectable hydrogel,
- Tumor vaccine,
- Fibrosis,
- Breast cancer metastasis,
- BRD4
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