Six CAR T cell therapies have received FDA approval, and several more are in the pipeline. However, these therapies carry serious and potentially fatal side effects, namely cytokine release syndrome (CRS) and neurotoxicity. These drawbacks manifest themselves in a range of symptoms, from high fever and vomiting to multivisceral failure and patient death, posing significant challenges for wider clinical application. Now, a research team has found a solution that could help CAR T therapies reach their full potential while minimizing serious side effects. Their findings are published in the journal Nature Materials. Undesirable interactions between CAR T and immune cells called macrophages lead to macrophage overactivation, resulting in the release of toxic cytokines leading to CRS and neurotoxicity. Controlling CAR T-macrophage interactions in vivo is challenging. Thus, the study introduces a materials engineering-based strategy of incorporating a sugar molecule into the surface of CAR T cells becoming “pegylated CAR T cells”. These sugars are then used as a reactive handle to create a biomaterial coating around these cells directly in the body, which acts as an “armor”, preventing dangerous interactions with macrophages.
