A new study in Engineering outlines live-cell glycocalyx engineering strategies aimed at improving adoptive cell therapies (ACTs) for B-cell lymphoma. The work focuses on addressing recurring ACT constraints—high manufacturing costs and limited antigen specificity—by modifying the tumor-cell interaction landscape at the cell-surface interface. By detailing techniques for manipulating the glycocalyx on therapeutic cells, the research points to a potentially more controllable way to optimize cell therapy performance without relying solely on antigen selection.