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Uncoupling CAR-T migration from cytotoxicity during serial killing

Technologies to assess CAR-T-cell serial killing in real-time got a big boost with the introduction of the xCELLigence RTCA eSight system. Advances in time-lapse microscopy and bioelectrical impedance have shed light on cytolytic activity in real time. However, the immediate close proximity of effector to target cells when CAR T cells are added to target cells can be a hindrance. As CAR Ts kill in a cooperative manner, they might only engage one-two targets in the entire assay. At lower effector:target ratios, the assay may reflect proliferative potential more than cytolytic potency. 

This webcast will present an innovative advance and first-of-its kind assay, leveraging the xCELLigence RTCA eSIGHT technology to combine imaging with impedance analyses and separate effector CAR T cells from their antigen-positive targets utilizing a layer of matrigel.

As matrigel has tuneable density, its composition can be matched to reflect the physiochemical properties of distinct stromal regions across several tumor microenvironments. Uncoupling migration from cytolytic activity yields enhanced translational insights into the energy cost of CAR-T-cell killing and potential biomarkers of CAR-T-cell potency prior to clinical endpoints.

Learn:

  • How CAR-T-cell migration can be measured independently from cytolytic activity during serial killing
  • What separating migration from killing reveals about CAR-T-cell energy use and potency
  • How tuneable matrigel models can better replicate tumor microenvironments to assess CAR-T function


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