Tumor lysates-constructed hydrogel to potentiate tumor immunotherapy.

Abstract

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.

• Authors: Xiangwu Chen, Zeyu Jiang, Yang Lin, Cancan Yu, Xinxin Nie, Guixiang Xu, Wei Xu, Yue Jiang, Yuxia Luan
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 358 Pg. 345-357 (06 2023) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 37150404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier B.V.

Chemical References

• Hydrogels
• Programmed Cell Death 1 Receptor

Topics

• Humans
• Hydrogels
• Programmed Cell Death 1 Receptor
• Neoplasms
• T-Lymphocytes (metabolism)
• Immunotherapy
• Tumor Microenvironment