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SB415286
JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Tumor lysates-constructed hydrogel to potentiate tumor immunotherapy

Xiangwu Chen,Zeyu Jiang,Yang Lin,Cancan Yu,Xinxin Nie,Guixiang Xu,Wei Xu,Yue Jiang,Yuxia Luan

T cell-based immunotherapy (TCBI) is an emerging approach to combat tumors. However, the outcome of TCBI is still far from satisfaction clinically, owing to stumbling blocks from insufficient immunogenicity , T cell exhaustion and immune evasion from programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway. Herein, an injectable tumor lysates-constructed hydrogel is reported to address these issues. Chemically modified tumor lysates are, for the first time, designed as the gelator to intratumorally construct hydrogel, achieving a robust antigen reservoir to induce strong immunogenicity. Meanwhile, hydrogel-encapsulated nicotinamide riboside and SB415286 enable strong mitophagy in T cells to prevent their exhaustion as well as powerfully genetical suppression of PD-1 expression to regulate immune evasion. Thus, our injectable hydrogel creates a robust immune niche within tumor, enabling to significantly potentiate TCBI. Our strategy pharmacologically regulates body's own T cells in situ, demonstrating potent immunotherapeutic effects and offering a conceptually new approach for TCBI.

CAS / MDL: 9005-38-3
研究领域: 肿瘤学 · 免疫学 · 药学
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