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纳米颗粒工程化 T 细胞的体内超声和光声成像及治疗后评估以指导过继性细胞免疫治疗

英文原题:In Vivo Ultrasound and Photoacoustic Imaging of Nanoparticle-Engineered T Cells and Post-Treatment Assessment to Guide Adoptive Cell Immunotherapy.

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In Vivo Ultrasound and Photoacoustic Imaging of Nanoparticle-Engineered T Cells and Post-Treatment Assessment to Guide Adoptive Cell Immunotherapy.

PubMed 2025/02/05(内容时间) ACS Nano Q1 · IF 17.3(JCR 2025)

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中文摘要

尽管前景广阔,过继性细胞疗法(ACT)在治疗大多数癌症,尤其是实体瘤方面仍然失败。为了指导开发并加速更有效的细胞免疫疗法的转化,需要先进的免疫成像工具来更好地理解在体内产生强健免疫应答的要求。甚至评估转移T细胞在肿瘤靶点的递送、位置和状态的方法也仍然缺乏。

因此,迫切需要一种实时、安全、无创、纵向的成像方法,以1)监测过继性T细胞的位置和状态,以及2)通过成像生物标志物评估治疗进展和应答。

在此,我们开发了一种结合超声(US)和光声(PA)成像的方法,能够在癌症免疫治疗的过继转移后实现T细胞追踪。我们的方法利用高度光稳定的金纳米棒和细胞表面工程来标记T细胞,而不影响效应功能,并生成用于转移后成像的PA对比。

我们的体内US/PA成像方法检测到纳米颗粒标记的T细胞在肿瘤处的积累,可视化了肿瘤体积的变化,并传达了伴随的血液生物标志物变化。US/PA数据还显示,在7天内,根据对T细胞疗法的阳性或阴性抗肿瘤应答,呈现出不同的趋势。结果突出了该方法的潜力,并推动了未来的开发,以扩展该平台用于先进的诊疗一体化免疫成像。

展开英文摘要原文

Despite great promise, adoptive cell therapy (ACT) continues to fail at treating a majority of cancers, especially solid tumors. To inform development and expedite the translation of more potent cellular immunotherapies, advanced immunoimaging tools are needed to better understand the in vivo requirements for generating a robust immune response. Even methods to evaluate the delivery, location, and status of transferred T cells at the tumor target are lacking.

Therefore, a real-time, safe, noninvasive, longitudinal imaging method is critically needed to 1) monitor adoptive T cell location and status and 2) assess treatment progression and response through imaging biomarkers.

Here, we developed a combined ultrasound (US) and photoacoustic (PA) imaging approach to enable T cell tracking following adoptive transfer for cancer immunotherapy.

Our approach leverages highly photostable gold nanorods and cell surface engineering to tag the T cells without impacting effector functions, as well as generate PA contrast for imaging post-transfer.

Our in vivo US/PA imaging approach detected nanoparticle-labeled T cell accumulation at the tumor, visualized changes in tumor volume, and conveyed accompanying changes in blood biomarkers. US/PA data also showed different trends according to a positive or negative antitumor response to T cell therapy over 7 days. Results highlight the potential of the approach and motivate future development to expand the platform for advanced, theranostic immunoimaging.

论文信息

作者
Kubelick KP、Kim J、Kim M、Huang X、Wang C、Song S、Xia Y、Emelianov SY
单位
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia 30332, United States.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
ACS nano2025 Feb 18
原文标识
PubMed 39908484 · DOI 10.1021/acsnano.4c12929