Nanotechnology is combining with T-cell biology to produce diagnostics and therapeutics that evade the immune system and deliver localized therapeutic payloads, which, through their tight targeting, minimize adverse side effects.
At TechConnect World’s recent “Nanotech” conference and expo in Anaheim, industry and academic researchers elaborated on the advances that are driving nanotechnology toward the clinic, including T-cell based delivery systems, the ability to design nanoparticles’ function and morphology, and new imaging options.
InCellerate, a new company formed by Laurence J. N. Cooper, M.D., Ph.D., director of pediatric cell therapy at M.D. Anderson Cancer Center, has been working on a high-throughput microelectroporation device—called HiTMeD—to electro-transfer RNA species to redirect T-cell specificity.
The device is also being designed to electro-transfer gold nanoparticles that can be functionalized to enhance T-cell biology. This combination generates T cells that can respond more rapidly and more robustly as a drug-delivery vehicle, thus having potential as a tumor-specific, adoptive immunotherapy.
“We see T cells as a vehicle for targeted delivery of nanoparticles to tissue sites,” Dr. Cooper said. Typically, the reticular endothelial system filters out infused nanoparticles. Wrapping the nanoparticles in T cells thwarts that. And, because chimeric antigen receptor (CAR) expression from mRNA will be temporary, InCellerate developed HiTMeD to make multiple infusions of these modified T cells practical.
T cells endogenously express a panel of receptors that orchestrate their ability to home to disease. InCellerate’s microelectroporation device essentially pokes holes in T cells so genes and/or nanoparticles can be inserted, thus turning the T cells into therapeutic or diagnostic vectors.
“This is different from therapy in which therapeutic genes are introduced using viruses,” Dr. Cooper stressed. The introduced gene enhances specificity to better eliminate malignant cells, while the nanoparticles add potency or imaging properties.
In targeting lung cancer, Dr. Cooper and his colleagues have introduced a CAR into T cells. This antigen receptor recognizes the CD19 molecule expressed on the cell surface of B-cell malignancies. Introducing the CAR as mRNA avoids integration into the T-cell chromosome and “avoids the potential genotoxicity associated with vector and transgene integration. In addition, the high-throughput capacity overcomes the expected transient CAR expression, as repeated rounds of electroporation can replace T cells that have lost transgene expression.”
HiTMeD can electroporate 2x108 cells within 10 minutes, ex vivo, according to Dr. Cooper. In tests, up to 80% of the primary T cells expressed the CD-19-specific CAR. This is at least a 10-fold improvement over other technologies, he added.