Clin Cancer Res: JAK1 inhibitor Itacitinib is effective in preventing cytokine release syndrome caused by CAR T cell therapy

Embedded antigen-insular (CAR) T-cells are a promising cancer immunotherapy treatment.
targeted therapy has shown good long-term recurrence rates in patients with B-cell leukemia and lymphoma.
, cytokine release syndrome (CRS) is a serious and potentially life-threatening side effect, usually associated with CAR-T cell therapy.
CRS is a rapid (ultra-fast) immune response driven by excessive release of inflammatory cytokines, including IFN, IFN-3, and IFN-6.
of the cytokines known to be involved in CRS play a role through the JAK-STAT signaling path.
study, the researchers analyzed the effects of blocking JAK signaling path pathps on CAR T cell proliferation, anti-tumor activity, and cytokine levels.
Itacitinib reduces cytokine levels in acute inflammatory mouse models Itacitinib reduces il6 Itacitinib produced by macrophages and reduces leukocyte production in CAR T cells.
Itacitinib did not affect the proliferation of PBMC or cytotoxic Itatinib did not reduce the anti-tumor activity of T cells, the researchers also found that when clinically relevant doses were used to simulate pharmacological inhibition of human JAK1, itacitinib did not significantly inhibit the proliferation or anti-tumor killing of three human CAR T cells.
, the anti-tumor activity of CD19-CAR T cells injected into the mouse decreased after oral itinib treatment of the immunodeficiency CD19 plus tumor mouse model.
, the results suggest that itacitinib may be used to prevent the occurrence of CAR-T cell-induced CRS.
Phase II trial (NCT04071366) to evaluate itacitinib's use to prevent CRS caused by CAR T cell therapy has been conducted.
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