Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL Biomaterials Pub Date : 2024-10-02 DOI:10.1016/j.biomaterials.2024.122871
Haimei Li , Zichen Wang , Yulin Hu , Guangqin He , Liang Huang , Yi Liu , Zhong Lin Wang , Peng Jiang
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Abstract

Chimeric antigen receptor (CAR) T cell therapy is a highly effective immunotherapy for hematological tumors, but its efficacy against most solid tumors remains challenging. Herein, a novel synergistic combination therapy of drug-free triboelectric immunotherapy and CAR-T cell therapy against solid tumor was proposed. A triboelectric nanogenerator (TENG) that can generate pulsed direct-current by coupling triboelectrification effect and electrostatic breakdown effect was fabricated. The TENG can generate up to 30 pulse direct-current peaks with peak current output ≈35 μA in a single sliding to power the triboelectric immunotherapy. The pulsed direct-current stimulation induced immunogenic cell death of tumor cells (survival rate of 35.9 %), which promoted dendritic cells maturation, accelerated the process of antigen presentation to CAR-T cells and enhanced the systemic adaptive immune response. Furthermore, triboelectric immunotherapy promoted M1-like macrophage polarization, reduced regulatory T cells differentiation and reprogrammed the tumor immunosuppressive microenvironment, which ultimately enhanced the efficacy of CAR-T cells to eradicate nearly 60 % of NALM6 solid tumor mass. Notably, considering that triboelectric immunotherapy is a safe and effective drug-free antitumor strategy, the combined therapy did not increase the burden of double-medication on patients.

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通过无药三电免疫疗法增强针对实体瘤的 CAR-T 细胞疗法。
嵌合抗原受体(CAR)T细胞疗法是一种治疗血液肿瘤的高效免疫疗法,但其对大多数实体瘤的疗效仍面临挑战。在此,我们提出了一种新型的无药三电免疫疗法与 CAR-T 细胞疗法联合治疗实体瘤的协同疗法。研究人员制作了一种三电纳米发电机(TENG),它能通过耦合三电化效应和静电击穿效应产生脉冲直流电。TENG 一次滑动可产生多达 30 个脉冲直流峰,峰值电流输出≈35 μA,为三电免疫疗法提供能量。脉冲直流电刺激诱导了肿瘤细胞的免疫原性死亡(存活率为 35.9%),促进了树突状细胞的成熟,加速了 CAR-T 细胞的抗原递呈过程,增强了全身适应性免疫反应。此外,三电免疫疗法还促进了 M1 类巨噬细胞的极化,减少了调节性 T 细胞的分化,重编程了肿瘤免疫抑制微环境,最终提高了 CAR-T 细胞的疗效,根除了近 60% 的 NALM6 实体瘤。值得注意的是,考虑到三电免疫疗法是一种安全有效的无药抗肿瘤策略,联合疗法不会增加患者的双重用药负担。
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来源期刊
Biomaterials
Biomaterials 工程技术-材料科学:生物材料
CiteScore
26.00
自引率
2.90%
发文量
565
审稿时长
46 days
期刊介绍: Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.
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