CAR T Cell Therapy Breakthrough: New Assay Reveals Membrane Architecture for Enhanced Efficacy
CAR T cell therapy has revolutionized cancer treatment, showing remarkable results in hematologic cancers. However, challenges persist, including antigen loss and limited success in solid tumors.
CAR T cells work by targeting and destroying cancer cells via tumor antigens like CD19 in B cell malignancies. A recent study using the Proximity Network Assay shed light on the spatial architecture of membrane proteins, such as CAR receptors, influencing T-cell signaling and therapeutic efficacy.
The assay efficiently detected CAR-positive cells in a mix containing 90% resting PBMCs and 10% CAR T cells. It provided quantitative and spatially resolved insights into surface receptor landscapes, capturing multiprotein domains, receptor clustering, and trogocytosis events. The CAR molecule showed significant colocalization with canonical signaling and adhesion proteins, indicating its incorporation into functional membrane domains.
The study investigated the membrane architecture of CD19-targeting CAR T cells in their resting state and during tumor engagement. It revealed that CAR T cells dynamically reconfigure their surface proteome during antigen engagement, with changes in protein expression and membrane remodeling. Trogocytosis, the acquisition of membrane fragments from tumor cells, was observed and quantified, shaping CAR T-cell phenotype and efficacy over time.
While CAR T cell therapy has shown promising results, understanding its membrane-based architecture and dynamics is crucial for improving its efficacy, particularly in solid tumors. The Proximity Network Assay offers valuable insights into these aspects, paving the way for further advancements in CAR T cell therapy.
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