New CAR T cell therapy approach minimizes severe side effects
In recent years, cancer researchers have hailed the arrival of chimeric antigen receptor T cell (CAR T) therapy, which has delivered promising results, transforming the fight against various forms of cancer. The process involves modifying patients' T-cells to target cancer cells, resulting in remarkable success rates for previously intractable forms of cancer.
Six CAR T cell therapies have secured FDA approval, and several more are in the pipeline. However, these therapies come with severe and potentially lethal side effects, namely cytokine release syndrome (CRS) and neurotoxicity. These drawbacks manifest as a range of symptoms-;from high fever and vomiting to multiple organ failure and patient death-;posing significant challenges to broader clinical application.
Now, a research team led by Michael Mitchell, associate professor in the School of Engineering and Applied Science at the University of Pennsylvania, has found a solution that could help CAR T therapies reach their full potential while minimizing severe side effects. Their findings are published in the journal Nature Materials.
The team says that their approach offers more than just a safety net for patients; it also opens up a new "therapeutic window" for treatment. This is made possible, Gong says, due to the size differences among tumor cells, CAR T cells, and macrophages. He says tumor cells and CAR T cells are typically smaller (ranging from 5-10 μm) compared to macrophages (>20 μm), and as the surface density of PEG on CAR T cells begins to dilute, interactions between CAR T cells and tumor cells are restored before interactions with macrophages.
This restoration says Mitchell allows CAR T cells to target and kill cancer cells without causing macrophage overactivation, thereby minimizing the risk of dangerous CRS symptoms and neurotoxic effects.
"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 says.
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