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Calibrated CAR Signaling Enables Low-Dose Therapy in Large B-Cell Lymphoma
Authors
Jae Park,M. Palomba
Karlo Perica,Sean Devlin,Gunjan Shah,Parastoo Dahi,Richard Lin,Gilles Salles,Michael Scordo,Andriy Derkach,Yannis Valtis,A. Lynch,Elizabeth Cathcart,Honglei Zhang,Heiko Schöder,Doris Leithner,Kelly Liotta,Alina Yu,Kelsey Stocker,Jia Li,Agnish Dey,Leopold Sellner,Reshma Singh,Varsha Sundaresan,Fengfei Zhao,Jorge Mansilla-Soto,Changhao He,Joel Meyerson,Kinga Hosszu,Devin McAvoy,Xiuyan Wang,Isabelle Rivière
+30 authors
,Michel SadelainPublished
Jul 2, 2024
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Abstract
We designed a CD19-targeted CAR comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3z and 4-1BB/CD3z CARs. Here we report the first-in-human, phase 1 clinical trial of 19(T2)28z-1XX CAR T cells in relapsed/refractory large B-cell lymphoma. We hypothesized that 1XX CAR T cells may be effective at low doses and investigated 4 doubling dose levels starting from 25x10
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