Kubelick Kelsey P, Kim Jinhwan, Kim Myeongsoo, Huang Xinyue, Wang Chenxiao, Song Seoyoon, Xia Younan, Emelianov Stanislav Y
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia 30332, United States.
School of Electrical & Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
ACS Nano. 2025 Feb 18;19(6):6079-6094. doi: 10.1021/acsnano.4c12929. Epub 2025 Feb 5.
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 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 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.
尽管过继性细胞疗法（ACT）前景广阔，但在治疗大多数癌症，尤其是实体瘤方面仍持续失败。为指导更有效的细胞免疫疗法的开发并加速其转化应用，需要先进的免疫成像工具来更好地了解产生强大免疫反应的要求。甚至连评估转移的T细胞在肿瘤靶点处的递送、位置和状态的方法都很缺乏。因此，迫切需要一种实时、安全、无创的纵向成像方法，以：1）监测过继性T细胞的位置和状态；2）通过成像生物标志物评估治疗进展和反应。在此，我们开发了一种超声（US）和光声（PA）联合成像方法，用于在癌症免疫治疗的过继转移后追踪T细胞。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，而不影响其效应功能，同时在转移后产生用于成像的PA对比度。我们的US/PA成像方法检测到纳米颗粒标记的T细胞在肿瘤处的聚集，可视化了肿瘤体积的变化，并显示了血液生物标志物的相应变化。US/PA数据还显示了在7天内对T细胞疗法的抗肿瘤反应为阳性或阴性时的不同趋势。结果突出了该方法的潜力，并推动了未来的发展，以扩展用于先进的治疗诊断免疫成像的平台。
