Controlling T cell–tumor cell interaction with a biomimetic physical barrier for cancer immunotherapy
Abstract
Cancer immunotherapy has shown tremendous promise in various cancers. However, current strategies, such as immune checkpoint blockade, primarily restore exhausted T cells but provide only transient efficacy, as the rapid clearance of antibodies. Their limited durability is further hindered by persistent T cell-tumor cell interactions that accelerate T cell exhaustion. To prevent T cells from sustained exposure to these interactions, we present a hydrogel-based biomimetic physical barrier (BPB) here to create a “protective zone” for T cells. The BPB temporarily blocks T cell-tumor cell interactions and shields T cells from inactivation and exhaustion, allowing them to accumulate and maintain their functional activity in the tumor microenvironment. After sufficient T cell accumulation, the dismantling of BPB triggered by near-infrared light irradiation-induced gel-sol transition will restore the interaction between T cells and tumor cells. This controlled re-exposure allows the accumulated T cells to attack the tumor cells in a more activated and anti-exhaustion state, maximizing their tumor-killing potential. Moreover, BPB not only enhances immediate tumor regression but also triggers systemic immune activation and durable memory responses, enabling long-term protection against tumor rechallenge and effective control of multifocal tumors. Collectively, our BPB for modulating the T cell-tumor cell interaction has great prospects for advancing cancer immunotherapy.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Yuxuan Zhang
College of Chemistry
Jinjin Wang
School of Pharmaceutical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences
Guangchao Qing
Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Yongchao Wang
Xianlei Li
Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Ting Luo
Yi-Feng Wang
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry
Lu Liu
Yufei Wang
Chemistry Division
Qiankun Ni
Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Shuyi Li
Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Junge Chen
Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Fangzhou Li
Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Weisheng Guo
Translational Medicine Center, Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences and The Second Affiliated Hospital, Guangzhou Medical University
Jinchao Zhang
State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry and Environmental Science, Hebei University
Ningqiang Gong
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Xing-Jie Liang
Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology