CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy.
Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy.
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嵌合抗原受体(CAR)T 细胞治疗是血液系统肿瘤的一种高效免疫疗法,但治疗大多数实体瘤仍面临挑战。本文提出一种用于实体瘤的新型协同联合疗法,将无药物摩擦电免疫治疗与 CAR-T 细胞治疗相结合。研究制备了一种摩擦纳米发电机(TENG),通过耦合摩擦起电效应和静电击穿效应产生脉冲直流电,为摩擦电免疫治疗供能。TENG 在一次滑动中可产生多达 30 个脉冲直流峰,峰值电流输出为 35 A。脉冲直流刺激可诱导肿瘤细胞发生免疫原性细胞死亡(存活率 35.9%),促进树突状细胞成熟,加快向 CAR-T 细胞呈递抗原,并增强全身适应性免疫应答。
此外,摩擦电免疫治疗促进 M1 样巨噬细胞极化、减少调节性 T 细胞分化并重塑肿瘤免疫抑制微环境,最终增强 CAR-T 细胞疗效,使其清除近 60% 的 NALM6 实体瘤肿瘤负荷。
值得注意的是,鉴于摩擦电免疫治疗是一种安全有效的无药物抗肿瘤策略,联合治疗并未增加患者双重用药的负担。
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 A 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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