In vivo imaging of nanoparticle-labeled CAR T cells

Abstract

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.

Multifunctional nanoparticle for cancer therapy

“… 461 , 462 , 463 The multifunctional nanoparticles are introduced ferromagnetism or paramagnetic for enhancing tumor therapy with MRI‐guiding. 464 , 465 , 466 There are some MRI contrast agents that have been used in clinical or are undergoing clinical trials based on multifunctional backbone for treatment cancer. For example, SPIONS is injected to track the drugs for MRI cellular imaging of hepatic parenchyma (NCT04682847); Ferrotran ® (a Fe 3 O 4 preparation) is used to virtual histology of the bladder wall for bladder cancer staging (NCT04369560); and ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are applied for measuring the activity of innate immune system within MS lesions (NCT05357833).…”

Nanodrugs Targeting T Cells in Tumor Therapy

“…NP have also been used to enable in vivo MRI of CAR-T cells: In two recent studies CAR-T cells were labeled with iron oxide-based spheric NP (Ø ~25 nm) ( 80 ) and nanoworms (Ø ~120 nm) ( 81 ). Luo and coworkers aimed to increase the stimulatory properties of CAR-T cells by binding interleukin-12 –coated human serum albumin-based NP onto the CAR-T cell surface by means of bioorthogenal chemistry ( 82 ).…”

Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters

“…Their target is the immune checkpoint molecule B7-H3 (CD276), a tumor antigen that is significantly upregulated in osteosarcoma [ 242 ]. This molecule is described to play a crucial role in T cell function inhibition [ 243 ]. Despite the advantages of CAR T cell therapy and its increasing usage in clinical practice in lymphomas and acute lymphocytic leukemia [ 244 ], its applicability in solid tumors presents multiple challenges [ 245 ].…”