In Vivo Tracking of Chimeric Antigen Receptor T-Cells

Chimeric antigen receptor (CAR) T-cell therapy is a specialized form of immunotherapy in which T-cells are engineered to track down, attack, and kill cancer cells in the body using an individual’s own immune system as a launch pad. To design these antigen receptors, T-cells are taken from the patient’s blood and modified to possess the gene for a receptor, giving the T-cells the ability to locate and attack specific cancer cell antigens. In general, CAR T-cell therapy is an effective treatment option for diseases like lymphoma and leukemia because of its ability to target these antigens on the cell surface. 

However, once these cells are injected back into the patient’s body, there is no reliable way to track their location and progress in locating and attacking tumors and other hematologic malignancies. While CAR T-cell immunotherapy provided impressive responses for the treatment of hematologic malignancies such as leukemia, the treatment of solid cancers has been less successful. This is in part because the CAR T-cells’ effectiveness and mechanisms against solid tumors is also a lesser understood topic. Scientists have been researching the ways these cells target solid tumors- whether they enter the physical tumor or surround its periphery. 

These lesser explored facets of CAR T-cell therapy are the research subject of Wei (Emma) Wu, a postdoctoral research fellow at the Daldrup-Link Lab in the Department of Radiology. In a recently published paper in Investigative Radiology, “Multimodal In Vivo Tracking of Chimeric Antigen Receptor T-Cells in Preclinical Glioblastoma Models,” Wu and her team describe their recent study working with iron oxide nanoparticles as CAR T-cell trackers. 

To monitor T-cells, Wu and her team labeled CAR T-cells with MegaPro-NP (nanoparticles) as a form of magnetic resonance imaging (MRI) contrast agents, as an alternative to previously used ferumoxytol, which has caused rare but severe anaphylactic reactions in patients. The accumulation of nanoparticle labeled CAR T-cells in the tumor tissue is reflected by hypointensity areas in MRI scanning. The accumulation of CAR T-cells in the tumor tissue correlated, as detected with MRI on day 3 after the infusion of the therapeutic cells, correlated with  a decline in tumor size at 1-2 weeks after treatment. Therefore, imaging the tumor accumulation of CAR T-cells with MRI can provide earlier diagnosis of tumor response to this new immunotherapy.

Together, Wu and her team have successfully shown that the new MegaPro nanoparticles can be used to label and track CAR T-cells in vivo. Being able to observe the nanoparticle-labeled CAR T-cells with MRI scan can provide researchers with a better understanding of how the underlying mechanisms of CAR T-cell therapy work. 


Top image: Rudy and Peter Skitterians from Pixabay

Bottom image: Emma Wu

March 2023