Novel PET, SPECT techniques help track, modify T cells for immunotherapy
With PET and single-photon emission computed tomography (SPECT), researchers have demonstrated that T cells can be modified with the antibody report 1 (DAbR1) gene to enable in vivo tracking for immunotherapy, according to research published online June 14 in the Journal of Nuclear Medicine.
Led by Simone Krebs, MD, an instructor of molecular imaging and therapy service at the Memorial Sloan Kettering Cancer Center in Ney York, the research team observed with the noninvasive techniques a great amount of blood distribution and high image contrast of the reporter gene.
"We have presented a novel T-cell tracking approach based on DOTA-lanthanoid antibody reporter with infinite affinity," Krebs et al. Wrote. "The high uptake as well as the prolonged and specific binding of radiolabeled AABD to the transduced T cells, and the low potential for immunogenicity, render DAbR1/AABD into a promising tool for monitoring the dynamics of adoptive cell therapies."
The researchers investigated whether DAbR1 can be expressed on lymphocytes and used as a reporter gene and suicide gene for therapy. They then utilized PET and SPECT imaging to successfully track genetically engineered T cells in vivo, according to the researchers.
"PET and SPECT co-registered with CT enable non-invasive, repetitive detection of radiotracer molecules at picomolar concentration and high spatial anatomical resolution," the researchers wrote. "These imaging modalities can provide exquisite sensitivity and specificity for detection of CAR T cells, once a CAR T cell specific reporter gene with high binding affinity for a molecular imaging agent and no expression in normal tissues has been developed."
The team sub-cloned DAbR1 together with green florescent protein into an SFG-retroviral vector, which was then used to transduce CD3/CD28-activated primary human T cells and second generation 1928z (CAR) T cells.
"Cell surface expression of DAbR1 was confirmed by cell update studies with radiolabeled AABD," the researchers wrote. "In addition, the feasibility of imaging of DAbR1 plus T cells in vivo after the injection of 86Y/177Lu AABD was studied and radiation doses determined."
Study results included the following, according to the researchers:
- A panel of DAbR1 expressing T cells and CAR T cells showed greater than eight-fold increased update of 86Y-AABD in vitro when compared to non-transduced cells.
- Imaging studies showed 86Y-AABD was retained by DAbR1 positive T cells while continuously clearing from normal tissues, allowing for in vivo tracking of CAR T cells.
- Normal organ dose estimates were favorable for repeated PET/CT studies.
- Selective T cell ablation in vivo with 177Lu-AABD seems feasible for clustered T cell populations.
A recent graduate from Dominican University (IL) with a bachelor’s in journalism, Melissa joined TriMed’s Chicago team in 2017 covering all aspects of health imaging. She’s a fan of singing and playing guitar, elephants, a good cup of tea, and her golden retriever Cooper.