First in Human Study of In-vivo Imaging of Ex-Vivo Labelled CAR T Cells with Dual PET-MR

Singla, Ritu; Wall, Dominic; Anderson, Susan; Zia, Nicholas; Korte, J.; Kravets, Lucy; McKiernan, Gregory; Butler, Jeanne; Gammilonghi, Amanda; Arora, Jyoti; Wright, Martin C.; Solomon, B.; Hicks, R.; Cain, Tim; Darcy, Phillip K.; Cullinane, Carleen; Neeson, Paul J.; Ramanathan, Rajesh; Shukla, Ravi; Bansal, Vipul; Harrison, S.

doi:10.1016/j.jcyt.2020.04.074

Cited by 2 publications

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“…In comparison, our study provided a microfluidics-based mechanical method for labeling human CAR T cells with ferumoxytol, and we used a multimodal approach to image intravenously infused CAR T cells labeled with iron in vivo in a preclinical model that has the potential for clinical translation. The feasibility for translation is demonstrated by the first in human study imaging CAR T cells labeled with copper-64 superparamagnetic iron oxide nanoparticles with dual PET-MR, which found that the functionality of the iron-labeled T cells was maintained and the labeled T cells remained persistent for an extended period of time in subjects ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

In vivo imaging of nanoparticle-labeled CAR T cells

Kiru

Zlitni

Tousley

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Metastatic osteosarcoma has a poor prognosis with a 2-y, event-free survival rate of ∼15 to 20%, highlighting the need for the advancement of efficacious therapeutics. Chimeric antigen receptor (CAR) T-cell therapy is a potent strategy for eliminating tumors by harnessing the immune system. However, clinical trials with CAR T cells in solid tumors have encountered significant challenges and have not yet demonstrated convincing evidence of efficacy for a large number of patients. A major bottleneck for the success of CAR T-cell therapy is our inability to monitor the accumulation of the CAR T cells in the tumor with clinical-imaging techniques. To address this, we developed a clinically translatable approach for labeling CAR T cells with iron oxide nanoparticles, which enabled the noninvasive detection of the iron-labeled T cells with magnetic resonance imaging (MRI), photoacoustic imaging (PAT), and magnetic particle imaging (MPI). Using a custom-made microfluidics device for T-cell labeling by mechanoporation, we achieved significant nanoparticle uptake in the CAR T cells, while preserving T-cell proliferation, viability, and function. Multimodal MRI, PAT, and MPI demonstrated homing of the T cells to osteosarcomas and off-target sites in animals administered with T cells labeled with the iron oxide nanoparticles, while T cells were not visualized in animals infused with unlabeled cells. This study details the successful labeling of CAR T cells with ferumoxytol, thereby paving the way for monitoring CAR T cells in solid tumors.

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Section: Discussionmentioning

confidence: 99%

In vivo imaging of nanoparticle-labeled CAR T cells

Kiru

Zlitni

Tousley

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“… 163 A recent first-in-human study investigated ex vivo labeling of CAR T cells targeting the carbohydrate Lewis Y antigen using Copper-64 labeled SPIO nanoparticles: these labeled cells were reinfused into patients with solid tumors and imaged using PET/MRI within 3–5 days to track the distribution of labeled cells to tumors and other body organs. 164 The addition of a PET label facilitated sensitive detection of the cells and MRI imaging enabled detection of the SPIO label while providing excellent delineation of soft tissue structures including the peripheral lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

MRI techniques for immunotherapy monitoring

Lau

Corrie²,

Gallagher³

2022

J Immunother Cancer

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MRI is a widely available clinical tool for cancer diagnosis and treatment monitoring. MRI provides excellent soft tissue imaging, using a wide range of contrast mechanisms, and can non-invasively detect tissue metabolites. These approaches can be used to distinguish cancer from normal tissues, to stratify tumor aggressiveness, and to identify changes within both the tumor and its microenvironment in response to therapy. In this review, the role of MRI in immunotherapy monitoring will be discussed and how it could be utilized in the future to address some of the unique clinical questions that arise from immunotherapy. For example, MRI could play a role in identifying pseudoprogression, mixed response, T cell infiltration, cell tracking, and some of the characteristic immune-related adverse events associated with these agents. The factors to be considered when developing MRI imaging biomarkers for immunotherapy will be reviewed. Finally, the advantages and limitations of each approach will be discussed, as well as the challenges for future clinical translation into routine clinical care. Given the increasing use of immunotherapy in a wide range of cancers and the ability of MRI to detect the microstructural and functional changes associated with successful response to immunotherapy, the technique has great potential for more widespread and routine use in the future for these applications.

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First in Human Study of In-vivo Imaging of Ex-Vivo Labelled CAR T Cells with Dual PET-MR

Cited by 2 publications

References 0 publications

In vivo imaging of nanoparticle-labeled CAR T cells

In vivo imaging of nanoparticle-labeled CAR T cells

MRI techniques for immunotherapy monitoring

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