Electroporation mechanism decreases life-threatening side effects of cancer treatment
Electroporation mechanism decreases life-threatening side effects of cancer treatment lead image
While chimeric antigen receptor (CAR) T-cell therapy is an effective cancer treatment, the inflammatory cytokine protein response (known as cytokine release syndrome, or CRS) is a life-threatening side effect that has hampered the treatment’s success.
Chen et al. created a microfluidic platform named AESOP (acoustic-electric shear orbiting poration) that can control the CAR gene dosage into T-cells to minimize the CRS response.
AESOP utilizes lateral cavity acoustic transducer technology, which creates the formation of nanopores on cellular membranes and allows cells to uptake the CAR gene (through mRNA). The dosage of the delivery is metered by pore size, which is controlled by electrical fields.
“By mixing the T-cells in between electric field exposures, we ensure that nanopores on the cell membrane are evenly expanded,” author Abraham Lee said. “The combination of uniform pores on the cell membranes and uniform mixing of cells with mRNA results in uniform delivery of mRNA into the cells.”
He compared the process to a washing machine, where a spinning drum evenly mixes detergent into each piece of clothing.
“For a high-performance washing machine, one can clean clothes thoroughly with the least amount of detergent. In this case we can uniformly deliver CAR mRNA into T cells at desired dosages that maximize treatment while avoiding CRS,” Lee said.
Lee emphasized the importance of calibrating the AESOP technology for each donor set.
“We did not anticipate the differences of T-cells among the donors,” he said. “Calibration can be automated in the future with AESOP technology, since one can modulate both the mechanical shear and the electric field to best match the donor cell population.”
Source: “Titrating chimeric antigen receptors on CAR T cells enabled by a microfluidic-based dosage-controlled intracellular mRNA delivery platform,” by Yu-Hsi Chen, Mahnoor Mirza, Ruoyu Jiang, and Abraham P. Lee, Biomicrofluidics (2024). The article can be accessed at https://doi.org/10.1063/5.0231595 .
This paper is part of the Selected Papers from IEEE-NANOMED 2023 Collection, learn more here .
