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Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35101971

RESUMO

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.


Assuntos
Neoplasias Ósseas , Óxido Ferroso-Férrico/farmacologia , Imunoterapia Adotiva , Imageamento por Ressonância Magnética , Nanopartículas/uso terapêutico , Neoplasias Experimentais , Osteossarcoma , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Animais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/terapia , Camundongos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/terapia , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/imunologia , Osteossarcoma/terapia
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