(391f) Magnetic Particle Imaging for Quantitative Tracking of Adoptive Cell Transfer in Cancer Immunotherapy

Adoptive cell transfer (ACT) is a cancer immunotherapy treatment that uses a cancer patient’s own T lymphocytes, which are expanded ex vivo, activated, and then infused with into the patient. ACT has emerged as an effective treatment for blood cancers, such as leukemias and lymphomas, but it has faced significant challenges when applied to solid tumors and cancers in privileged locations, such as the brain. Glioblastoma (GBM) is the most common and aggressive cancer of the central nervous system in adults, with a dismal prognosis of 15-18 month average patient survival after diagnosis. The optimal delivery route of ACT for the treatment of GBM remains an important and unanswered question. Most ongoing immunotherapy clinical trials deliver adoptively transferred T cells intravenously, but their accumulation in brain tumors is regulated by the blood-brain barrier, potentially diminishing treatment effectiveness.

In the context of cell therapies, in vivo biomedical imaging has been used to track cells delivered in preclinical disease models using two general approaches: (i) genetic modification of cells to express a marker that enables optical visualization (IVIS®) or nuclear tomographic imaging (PET/SPECT) and (ii) labeling of cells using particles that provides contrast (MRI) or generate a signal suitable for imaging (IVIS®, PET/SPECT). Each of those imaging modalities has its advantages and disadvantages. The innovation of the present study lies in the use of a novel and powerful molecular imaging technology, Magnetic Particle Imaging (MPI), that can unambiguously and spatially detect and quantify iron oxide magnetic tracers in vivo. Because the tracer is not normally found in the body, MPI images have excellent contrast, sensitivity, and sub-millimeter resolution.

Here, we report the successful labeling of T-cells with magnetic nanoparticles and tracking using MPI. We demonstrate that mouse cytotoxic and tumor-specific T-cells can be magnetically labeled with ferucarbotran nanoparticles and tracked using MPI without affecting cell viability, phenotype, or cell function. Nanoparticle loading in the cells could be controlled through incubation conditions and did not impact T-cell viability or metabolic activity. Furthermore, the phenotypic and functional activities of T-cells were unchanged at all tested incubation conditions demonstrating that nanoparticle loading do not affect T-cells. Labeled T-cells had cytotoxic activity and released interferon gamma when co-cultured with murine KR158B-Luc gp100 glioblastoma cells, similar to unlabeled T cells. Moreover, the internalized iron oxide nanoparticles can be quantified and spatially detected using MPI both in vitro and in vivo in a preclinical murine glioblastoma model.

The use of MPI to track the cells utilized in cancer immunotherapies will allow the better understanding of those therapy dynamics and help to further optimize delivery routes and treatment effectiveness against glioblastoma and other cancers.