Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia (original) (raw)

“…We and other groups have also noted investigational cytokine activation profiles which correlate with clinical syndrome of CRS [1][2][3][4]6,32]. Effector cytokines such as INFÇ and soluble interleukin-2 receptor a (sIL2Ra) are elevated but so are cytokines traditionally associated with macrophage activation such as IL-6 and interleukin-10.…”

Section: Toxicitymentioning

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“…We and other groups have also noted investigational cytokine activation profiles which correlate with clinical syndrome of CRS [1][2][3][4]6,32]. Effector cytokines such as INFÇ and soluble interleukin-2 receptor a (sIL2Ra) are elevated but so are cytokines traditionally associated with macrophage activation such as IL-6 and interleukin-10.…”

Section: Toxicitymentioning

“…While children are initially more responsive to traditional salvage chemotherapy approaches than adults, these remissions are often not sustained and relapsed ALL remains a leading cause of cancer deaths in children [29,30]. It is this dismal prognosis and lack of conventional treatment options, which underscores the impact of the dramatic responses observed with CD19-CAR T-cell therapy in patients with relapsed and refractory ALL [1,3,4,31,32].…”

Section: Clinical Outcomes Of Cd19-car T-cell Therapymentioning

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“…The severity of CRS does not appear to correlate with overall disease response, but most responding patients demonstrate some degree of CRS. [3][4][5][6][7] In patients with acute lymphoblastic leukemia (ALL), CRS has been correlated with disease burden at the time of infusion, and experience has demonstrated that more potent conditioning regimens may increase the likelihood of severe CRS and/or CAR-related toxicity. 8 Patients with severe CRS can also develop a macrophage activation syndrome (MAS) reminiscent of hemophagocytic lymphohistiocytosis, as demonstrated by overlapping cytokine profiles, hyperferritinemia, and evidence of hemophagocytosis on bone marrow biopsy.…”

Section: Bystander Innate Cellsmentioning

“…1–5 CARs contain an extracellular ScFv fragment recognizing tumor-associated antigens (TAAs), the CD3z intracellular T cell-activating domain and co-stimulatory domains such as those derived from CD28 and 4-1BB. Upon binding of target antigens by ScFv, the signaling domains are activated, leading to target cell killing and CAR-T cell proliferatio.…”

Section: Introductionmentioning