학술논문

Tumor lysing genetically engineered T cells loaded with multi-modal imaging agents.
Document Type
article
Source
Scientific reports. 4(1)
Subject
T-Lymphocytes
Humans
Receptors
Antigen
T-Cell
Recombinant Fusion Proteins
Antigens
CD19
Contrast Media
Radiopharmaceuticals
Positron-Emission Tomography
Magnetic Resonance Imaging
Adoptive Transfer
Electroporation
Cell Survival
Protein Binding
Molecular Imaging
Cell Tracking
Antigens
CD19
Receptors
Antigen
T-Cell
Language
Abstract
Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION-(64)Cu). This can now be potentially used for (64)Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR(+)SPION(pos) T cells effectively target in vitro CD19(+) lymphoma.