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Apoptotic cells therapy for the prevention of cytokine release syndrome (CRS) in CAR T-cell therapy

      Allocetra™ (Enlivex Therapeutics Ltd.) is a cell-based therapy composed of donor mononuclear-enriched leukocytes, containing early apoptotic cells with no necrotic cells. It was shown as safe and potentially efficacious for the prevention of aGVHD in patients with hematologic malignancies (Mevorach et al. BBMT 2014). Chimeric antigen receptor (CAR)-modified T cells with specificity against CD19 have shown promise in highly refractory hematologic malignancies, albeit with significant toxicity. 30% of patients with acute lymphoblastic leukemia develop severe forms of CRS and possibly related neurotoxicity. CRS resembles macrophage-activating syndrome and hemophagocytosis in response to CAR T-secreting IFN-g and possibly added cytokines. We tested the effects of early apoptotic cells on CRS and CAR T cell cytotoxicity.
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