RT Journal Article
SR Electronic
T1 Tracking Adoptive T Cell Therapy Using Magnetic Particle Imaging
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.02.128587
DO 10.1101/2020.06.02.128587
A1 Angelie Rivera-Rodriguez
A1 Lan B. Hoang-Minh
A1 Andreina Chiu-Lam
A1 Nicole Sarna
A1 Leyda Marrero-Morales
A1 Duane A. Mitchell
A1 Carlos Rinaldi
YR 2020
UL http://biorxiv.org/content/early/2020/06/03/2020.06.02.128587.abstract
AB Adoptive 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.Competing Interest StatementThe authors declare the following competing financial interest(s): D.A.M. has patented immunotherapy related technologies that have been licensed by Annias Immunotherapeutics, Inc., Immunomic Therapeutics, Inc., Celldex Therapeutics, Inc., and iOncologi, Inc. D.A.M. receives research funding from Immunomic Therapeutics, serves as a consultant/advisor to Tocagen, Inc., and is co-founder of iOncologi, Inc., a biotechnology company specializing in immuno-oncology. The other authors declare no conflicts.