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.

 

Comments:

The passage describes a novel approach to improving T cell-based immunotherapy (TCBI) for tumor treatment. The current limitations of TCBI are identified as insufficient immunogenicity, T cell exhaustion, and immune evasion through the PD-1/PD-L1 pathway. To address these challenges, the researchers have developed an injectable hydrogel constructed using chemically modified tumor lysates.

The tumor lysates, which are modified to act as gelators, are used to form a hydrogel within the tumor when injected. This hydrogel serves as a reservoir of antigens, enhancing the immunogenicity of the tumor. By presenting a large amount of tumor-specific antigens, the hydrogel stimulates a strong immune response.

Additionally, the hydrogel contains two key components: nicotinamide riboside and SB415286. These components promote mitophagy in T cells, preventing their exhaustion. Mitophagy is a process by which damaged mitochondria are removed from cells, allowing T cells to maintain their function and prevent exhaustion.

Furthermore, the hydrogel facilitates the genetic suppression of PD-1 expression, which is a checkpoint molecule involved in immune evasion. By reducing PD-1 expression, the hydrogel helps to regulate immune evasion mechanisms employed by tumors.

Overall, the injectable hydrogel described in the passage aims to create an immune-activating environment within the tumor, addressing the limitations of TCBI. The strategy enhances the immunotherapeutic effects of TCBI by promoting immunogenicity, preventing T cell exhaustion, and regulating immune evasion. This approach represents a conceptually new way to potentiate T cell-based immunotherapy for tumor treatment.

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