Tracking Adoptive T Cell Therapy Using Magnetic Particle Imaging

Abstract

ABSTRACTAdoptive cellular therapy (ACT) is a potent strategy to boost the immune response against cancer. ACT is an effective treatment for blood cancers, such as leukemias and lymphomas, but faces challenges treating solid tumors and cancers in locations like the brain. A critical step for success of ACT immunotherapy is achieving efficient trafficking of T cells to solid tumors, and the non-invasive and quantitative tracking of adoptively transferred T cell biodistribution would accelerate its development. Here, we demonstrate the use of Magnetic Particle Imaging (MPI) to non-invasively track ACT T cells in vivo. Labeling T cells with the superparamagnetic iron oxide nanoparticle tracer ferucarbotran did not affect T cell viability, phenotype, or cytotoxic function in vitro. Following ACT, ferucarbotran-labeled T cells were detected and quantified using MPI ex vivo and in vivo, in a mouse model of invasive brain cancer. Proof-of-principle in vivo MPI demonstrated its capacity to detect labeled T cells in lungs and liver after intravenous administration and to monitor T cell localization in the brain after intraventricular administration. Ex vivo imaging using MPI and optical imaging suggests accumulation of systemically administered ferucarbotran-labeled T cells in the brain, where MPI signal from ferucarbotran tracers and fluorescently tagged T cells were observed. Ex vivo imaging also suggest differential accumulation of nanoparticles and viable T cells in other organs like the spleen and liver. These results support the use of MPI to track adoptively transferred T cells and accelerate the development of ACT treatments for brain tumors and other cancers.