Multimodal In Vivo Tracking of Chimeric Antigen Receptor T Cells in Preclinical Glioblastoma Models

Wu, Wei Emma; Chang, Edwin; Jin, Linchun; Liu, Shiqin; Huang, Ching‐Hsin; Kamal, Rozy; Liang, Tie; Aissaoui, Nour Mary; Theruvath, Ashok J.; Pisani, Laura; Moseley, Michael E.; Stoyanova, Tanya; Paulmurugan, Ramasamy; Huang, Jianping; Mitchell, Duane A.

doi:10.1097/rli.0000000000000946

Cited by 8 publications

(9 citation statements)

References 34 publications

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“…This is consistent with safety reports of other IOPs with similar hydrodynamic diameters 36 . A recent study from our group demonstrated that IOP could be used for ex vivo labeling and in vivo tracking of CAR T cells in a mouse model of glioblastoma 37 . First in-human clinical trials used IOP as a liver contrast agent (NCT03407495).…”

Section: Discussionsupporting

confidence: 84%

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy

Roudi,

Pisani,

Pisani

et al. 2023

Invest Radiol

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Objectives A novel clinically translatable iron oxide nanoparticle (IOP) is currently being tested in phase 2 clinical trials as a magnetic resonance imaging (MRI) contrast agent for hepatocellular carcinoma diagnosis. The purpose of our study is to evaluate if this IOP can detect activation of tumor-associated macrophages (TAMs) due to CD47 mAb-targeted immunotherapy in 2 mouse models of osteosarcoma. Materials and Methods The toxicity, biodistribution, and pharmacokinetics of IOP were evaluated in 77 female and 77 male rats. Then, 24 female BALB/c mice with intratibial murine K7M2 tumors and 24 female NOD scid gamma mice with intratibial human 143B osteosarcoma xenografts were treated with either CD47 mAb (n = 12) or control antibody (n = 12). In each treatment group, 6 mice underwent MRI scans before and after intravenous infusion of either IOP or ferumoxytol (30 mg Fe/kg). Tumor T2* values and TAM markers F4/80, CD80, CD206, and Prussian blue staining were compared between different experimental groups using exact 2-sided Wilcoxon rank sum tests. Results Biodistribution and safety evaluations of IOP were favorable for doses of less than 50 mg Fe/kg body weight in female and male rats. Both IOP and ferumoxytol caused negative enhancement (darkening) of the tumor tissue. Both murine and human osteosarcoma tumors treated with CD47 mAb demonstrated significantly shortened T2* relaxation times after infusion of IOP or ferumoxytol compared with controls (all P's < 0.05). Higher levels of F4/80+CD80+ were found in murine and human osteosarcomas treated with CD47 mAb compared with sham-treated controls (all P's < 0.05). In addition, murine CD47 mAb-treated tumors after infusion of either IOP or ferumoxytol showed significantly higher numbers of Prussian blue–positive cells compared with controls (P < 0.05). There was no significant difference of F4/80+CD206+ cells among any of the groups (all P's > 0.05). Conclusions Iron oxide nanoparticle–enhanced MRI can be used to diagnose CD47 mAb-mediated TAM-activation in osteosarcomas.

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Section: Discussionsupporting

confidence: 84%

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy

Roudi,

Pisani,

Pisani

et al. 2023

Invest Radiol

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“…As we demonstrate in this work, MPI to addresses the limitations of current cellular imaging techniques. MPI specifically identifies the location of iron-labeled cells and produces a specific (hotspot) image 31–38 , similar to images obtained by 19 F MRI and nuclear imaging. Here, we demonstrate that MPI also offers high resolution to determine cellular location.…”

Section: Discussionmentioning

confidence: 86%

“…Most MPI cell tracking studies have been performed with adherent cell types, such as stem cells 31,32 , dendritic cells 33,34 , cancer cells 35 , and macrophages 36 . There is a growing desire to track T cells and NK cells, which unlike stem, dendritic and cancer cells, are non-adherent (suspension) cells 37,38 . These pose additional challenges such as: first, suspension cells tend to be less phagocytic to iron oxide nanoparticles leading to lower MPI sensitivity, and second, it is more challenging to eliminate free iron from suspension cells post-labeling.…”

Section: Introductionmentioning

confidence: 99%

Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging

Sehl,

Yang,

Anjier

et al. 2024

Preprint

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Introduction: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells. Methods: Human-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours then the excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled vs. unlabeled NK-92 cells was assessed after 4 hours of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17) using bioluminescent or GFP counts. Labeled NK-92 cells at two different doses (0.5 or 1 x 10^6) were administered to excised mouse brains (cerebellum), tibias, and lungs then imaged by 3D preclinical MPI (MOMENTUM imager) and localized relative to fiducial markers. NK-92 cells were imaged by clinical-scale MPI under development at Magnetic Insight Inc. Results: NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measured effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of VivoTrax-labeled NK-92 cells, with preclinical limit of detection of 3.1 x 10^4 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, tibias, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection of a clinically relevant dose of 4 x 10^7 labeled NK-92 cells was demonstrated on clinical-scale MPI. Conclusion: MPI can provide sensitive, quantitative, and accurate spatial information on NK cell delivery, showing its potential to resolve a significant unmet clinical need to track NK cell treatments in patients.

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Section: Discussionmentioning

confidence: 99%

“…A recent study from our group showed that MegaPro nanoparticles could be used for in vivo tracking of CAR T cells in a mouse model of glioblastoma [30]. The integration of non-invasive MR imaging with MegaPro into clinical practice may provide a potential approach to identifying individuals who are more likely to benefit from novel CAR T-cell immunotherapies in the future [30]. The use of a clinical 3T scanner in the present large animal study represents a robust tool for translational research, augmenting the reproducibility and comparability of our findings.…”

Section: Discussionmentioning

confidence: 99%

MegaPro, a clinically translatable nanoparticle for in vivo tracking of stem cell implants in pig cartilage defects

Suryadevara¹,

Hajipour²,

Adams³

et al. 2023

Theranostics

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Rationale: Efficient labeling methods for mesenchymal stem cells (MSCs) are crucial for tracking and understanding their behavior in regenerative medicine applications, particularly in cartilage defects. MegaPro nanoparticles have emerged as a potential alternative to ferumoxytol nanoparticles for this purpose. Methods: In this study, we employed mechanoporation to develop an efficient labeling method for MSCs using MegaPro nanoparticles and compared their effectiveness with ferumoxytol nanoparticles in tracking MSCs and chondrogenic pellets. Pig MSCs were labeled with both nanoparticles using a custom-made microfluidic device, and their characteristics were analyzed using various imaging and spectroscopy techniques. The viability and differentiation capacity of labeled MSCs were also assessed. Labeled MSCs and chondrogenic pellets were implanted into pig knee joints and monitored using MRI and histological analysis. Results: MegaPro-labeled MSCs demonstrated shorter T2 relaxation times, higher iron content, and greater nanoparticle uptake compared to ferumoxytol-labeled MSCs, without significantly affecting their viability and differentiation capacity. Post-implantation, MegaPro-labeled MSCs and chondrogenic pellets displayed a strong hypointense signal on MRI with considerably shorter T2* relaxation times compared to adjacent cartilage. The hypointense signal of both MegaPro-and ferumoxytol-labeled chondrogenic pellets decreased over time. Histological evaluations showed regenerated defect areas and proteoglycan formation with no significant differences between the labeled groups. Conclusion:Our study demonstrates that mechanoporation with MegaPro nanoparticles enables efficient MSC labeling without affecting viability or differentiation. MegaPro-labeled cells show enhanced MRI tracking compared to ferumoxytol-labeled cells, emphasizing their potential in clinical stem cell therapies for cartilage defects.

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Multimodal In Vivo Tracking of Chimeric Antigen Receptor T Cells in Preclinical Glioblastoma Models

Cited by 8 publications

References 34 publications

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy

Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging

MegaPro, a clinically translatable nanoparticle for in vivo tracking of stem cell implants in pig cartilage defects

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