Tumor lysates-constructed hydrogel to potentiate tumor immunotherapy

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.

Automated summary

An injectable hydrogel constructed from tumor lysates has been developed to address the challenges in T cell-based immunotherapy, such as low immunogenicity, T cell exhaustion, and immune evasion through the PD-1/PD-L1 pathway. The hydrogel provides a robust antigen reservoir to induce strong immunogenicity within the tumor, while also preventing T cell exhaustion through mitophagy and suppressing PD-1 expression to regulate immune evasion. This strategy significantly enhances T cell-based immunotherapy and offers a new approach for cancer treatment.