CAR-T-cell monitoring using specific multimers: a fast and specific method allowing uniform evaluation

CAR-T cell immunotherapy is used successfully against refractory hematological and solid cancer. Cellular Monitoring of CAR-T cells is important both for validating expression of the CAR construct in the transduced T cells prior to infusion, and persistence of the CAR-T cells in the blood of the recipient. CAR expression is often detected by fluorochrome conjugated antibody against a structural part of the CAR construct, and not the specific target for the CAR interaction. We have developed a flexible platform to manufacture direct CAR-T cells detecting multimer reagents, CAR-Dextramer® allowing detection of CAR-T cells of different specificities and affinities Activation of chimeric antigen receptor T (CAR-T) cells are critical for ensuring therapeutic efficacy in adoptive immunotherapy. CAR-T cell activation requires two signals: antigen recognition through the CAR and co-stimulation via intracellular interactions, and by stimulatory molecules such as interleukins. Control of activation and continuous monitoring are essential to optimize potency to improve clinical outcomes in hematologic and solid tumors immunotherapy. We have developed CAR-T cell activation reagents based on the CAR-Dextramer® scaffold, that contain said stimulatory molecules. These reagents can be used to evaluate the ability of the transduced CAR-T cells to be stimulated or expanded through the specific interaction with its cognate target, and costimulatory signals.