incb039110 has been researched along with Cytokine-Release-Syndrome* in 1 studies
1 other study(ies) available for incb039110 and Cytokine-Release-Syndrome
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Itacitinib (INCB039110), a JAK1 Inhibitor, Reduces Cytokines Associated with Cytokine Release Syndrome Induced by CAR T-cell Therapy.
T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown long-term relapse-free survival in patients with B-cell leukemia and lymphoma. However, cytokine release syndrome (CRS) represents a serious, potentially life-threatening side effect often associated with CAR T-cell therapy. CRS manifests as a rapid (hyper)immune reaction driven by excessive inflammatory cytokine release, including IFNγ and IL6.. Many cytokines implicated in CRS are known to signal through the JAK-STAT pathway. Here we study the effect of blocking JAK pathway signaling on CAR T-cell proliferation, antitumor activity, and cytokine levels in. We report that itacitinib, a potent, selective JAK1 inhibitor, was able to significantly and dose-dependently reduce levels of multiple cytokines implicated in CRS in several. Together, these data suggest that itacitinib has potential as a prophylactic agent for the prevention of CAR T cell-induced CRS, and a phase II clinical trial of itacitinib for prevention of CRS induced by CAR T-cell therapy has been initiated (NCT04071366). Topics: Animals; Apoptosis; Azetidines; Cell Proliferation; Cytokine Release Syndrome; Cytokines; Female; Humans; Immunotherapy, Adoptive; Isonicotinic Acids; Janus Kinase 1; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured; Xenograft Model Antitumor Assays | 2020 |