The process of CAR T cell immunotherapy involves modifying patients’ T-cells to target cancer cells, resulting in remarkable success rates for forms of cancer that previously had no treatment. However, these therapies come with severe and potentially lethal side effects, including cytokine release syndrome (CRS) and neurotoxicity.
To solve this problem, a research team led by Michael Mitchell, PhD, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering (BE), developed a new materials engineering-based strategy.
The new method involves attaching a sugar molecule onto the surface of CAR T cells using metabolic labeling, a modification that enables the CAR T cells to attack cancer cells without any hindrance. When symptoms of CRS arise, the team introduces another molecule, polyethylene glycol (PEG), to create a “suit of armor,” which effectively blocks dangerous interactions between the engineered T cells, macrophages, and the tumor cells themselves.
The research team says that in addition to offering a safety net for patients, their approach also opens up a new “therapeutic window” for treatment.
“By incorporating the PEG buffer, we’ve successfully managed to modulate the interactions between CAR T cells and macrophages. This enables a therapy that is both safer and effective,” Mitchell said in Penn Today. He also stated, “The implications could be far-reaching. We’re looking at a potentially universal approach to making cellular therapies safer for all patients.”
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