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Updated: May 29, 2025
Whole-animal Imaging and Flow Cytometric Techniques for Analysis of Antigen-specific CD8+ T Cell Responses after Nanoparticle Vaccination
Published on: April 29, 2015
In Vivo Ultrasound and Photoacoustic Imaging of Nanoparticle-Engineered T Cells and Post-Treatment Assessment to
Kelsey P Kubelick1,2, Jinhwan Kim1,2, Myeongsoo Kim1
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia 30332, United States.
Abstract:
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.
Insights
Advanced ultrasound and photoacoustic imaging tracks cancer-fighting T cells in real-time. This novel immunoimaging approach monitors T cell therapy effectiveness and aids in developing better cancer treatments.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunotherapy
Background:
- Adoptive cell therapy (ACT) shows promise but struggles with solid tumors.
- Effective cancer immunotherapy requires understanding T cell behavior in vivo.
- Current methods lack safe, noninvasive ways to track T cells and assess treatment response.
Purpose of the Study:
- To develop a real-time, noninvasive imaging method for tracking T cells after adoptive transfer.
- To monitor T cell location, status, and treatment progression using imaging biomarkers.
- To improve the development and translation of cellular immunotherapies.
Main Methods:
- Developed a combined ultrasound (US) and photoacoustic (PA) imaging approach.
- Engineered T cells with gold nanorods for PA contrast without affecting function.
- Utilized US/PA imaging to track nanoparticle-labeled T cells in vivo.
Main Results:
- Successfully detected nanoparticle-labeled T cell accumulation at tumor sites.
- Visualized changes in tumor volume and correlated them with blood biomarkers.
- Observed distinct US/PA imaging trends correlating with positive or negative antitumor responses over 7 days.
Conclusions:
- The developed US/PA imaging platform enables longitudinal tracking of adoptive T cells.
- This approach can assess treatment progression and response, offering potential for theranostic immunoimaging.
- Highlights the need for advanced imaging tools to optimize cancer immunotherapy.
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