Cellular and molecular imaging of CAR-T cell-based immunotherapy

doi:10.1016/j.addr.2023.115135

Review

. 2023 Dec:203:115135.

doi: 10.1016/j.addr.2023.115135. Epub 2023 Nov 4.

Cellular and molecular imaging of CAR-T cell-based immunotherapy

Longwei Liu¹, Chi Woo Yoon², Zhou Yuan², Tianze Guo², Yunjia Qu³, Peixiang He³, Xi Yu², Ziyue Zhu², Praopim Limsakul⁴, Yingxiao Wang⁵

Affiliations

¹ Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA. Electronic address: longweil@usc.edu.
² Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
³ Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA.
⁴ Division of Physical Science, Faculty of Science and Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
⁵ Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: ywang283@usc.edu.

PMID: 37931847
PMCID: PMC11052581 (available on 2024-12-01)
DOI: 10.1016/j.addr.2023.115135

Review

Cellular and molecular imaging of CAR-T cell-based immunotherapy

Longwei Liu et al. Adv Drug Deliv Rev. 2023 Dec.

. 2023 Dec:203:115135.

doi: 10.1016/j.addr.2023.115135. Epub 2023 Nov 4.

Authors

Longwei Liu¹, Chi Woo Yoon², Zhou Yuan², Tianze Guo², Yunjia Qu³, Peixiang He³, Xi Yu², Ziyue Zhu², Praopim Limsakul⁴, Yingxiao Wang⁵

Affiliations

¹ Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA. Electronic address: longweil@usc.edu.
² Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
³ Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA.
⁴ Division of Physical Science, Faculty of Science and Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
⁵ Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: ywang283@usc.edu.

PMID: 37931847
PMCID: PMC11052581 (available on 2024-12-01)
DOI: 10.1016/j.addr.2023.115135

Abstract

Chimeric Antigen Receptor T cell (CAR-T) therapy has emerged as a transformative therapeutic strategy for hematological malignancies. However, its efficacy in treating solid tumors remains limited. An in-depth and comprehensive understanding of CAR-T cell signaling pathways and the ability to track CAR-T cell biodistribution and activation in real-time within the tumor microenvironment will be instrumental in designing the next generation of CAR-T cells for solid tumor therapy. This review summarizes the signaling network and the cellular and molecular imaging tools and platforms that are utilized in CAR-T cell-based immune therapies, covering both in vitro and in vivo studies. Firstly, we provide an overview of the existing understanding of the activation and cytotoxic mechanisms of CAR-T cells, compared to the mechanism of T cell receptor (TCR) signaling pathways. We further describe the commonly employed tools for live cell imaging, coupled with recent research progress, with a focus on genetically encoded fluorescent proteins (FPs) and biosensors. We then discuss the utility of diverse in vivo imaging modalities, including fluorescence and bioluminescence imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and photoacoustic (PA) imaging, for noninvasive monitoring of CAR-T cell dynamics within tumor tissues, thereby providing critical insights into therapy's strengths and weaknesses. Lastly, we discuss the current challenges and future directions of CAR-T cell therapy from the imaging perspective. We foresee that a comprehensive and integrative approach to CAR-T cell imaging will enable the development of more effective treatments for solid tumors in the future.

Keywords: Biosensors; CAR-T; Immune therapy; In vivo CAR-T imaging; Live cell imaging.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Han SY, Zhao ZX, Wu J. Han SY, et al. Mil Med Res. 2024 Feb 3;11(1):12. doi: 10.1186/s40779-024-00517-8. Mil Med Res. 2024. PMID: 38308320 Free PMC article. No abstract available.

References

1. Davila ML et al., Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science translational medicine 6, 224ra225 (2014). - PMC - PubMed
1. Grupp SA et al., Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368, 1509–1518 (2013). - PMC - PubMed
1. Morgan RA et al., Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Molecular therapy : the journal of the American Society of Gene Therapy 18, 843–851 (2010). - PMC - PubMed
1. Maus MV, Grupp SA, Porter DL, June CH, Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123, 2625–2635 (2014). - PMC - PubMed
1. Chakravarti D, Wong WW, Synthetic biology in cell-based cancer immunotherapy. Trends Biotechnol 33, 449–461 (2015). - PMC - PubMed

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[1] Davila ML et al., Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science translational medicine 6, 224ra225 (2014). - PMC - PubMed

[2] Davila ML et al., Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science translational medicine 6, 224ra225 (2014). - PMC - PubMed

[3] Grupp SA et al., Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368, 1509–1518 (2013). - PMC - PubMed

[4] Grupp SA et al., Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368, 1509–1518 (2013). - PMC - PubMed

[5] Morgan RA et al., Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Molecular therapy : the journal of the American Society of Gene Therapy 18, 843–851 (2010). - PMC - PubMed

[6] Morgan RA et al., Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Molecular therapy : the journal of the American Society of Gene Therapy 18, 843–851 (2010). - PMC - PubMed

[7] Maus MV, Grupp SA, Porter DL, June CH, Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123, 2625–2635 (2014). - PMC - PubMed

[8] Maus MV, Grupp SA, Porter DL, June CH, Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123, 2625–2635 (2014). - PMC - PubMed

[9] Chakravarti D, Wong WW, Synthetic biology in cell-based cancer immunotherapy. Trends Biotechnol 33, 449–461 (2015). - PMC - PubMed

[10] Chakravarti D, Wong WW, Synthetic biology in cell-based cancer immunotherapy. Trends Biotechnol 33, 449–461 (2015). - PMC - PubMed

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Cellular and molecular imaging of CAR-T cell-based immunotherapy

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Cellular and molecular imaging of CAR-T cell-based immunotherapy

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