Calibrated CAR Signaling Enables Low-Dose Therapy in Large B-Cell Lymphoma.

Journal: Research Square
Published:
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 25×106 CAR T cells. The overall response rate (ORR) was 82% and complete response (CR) rate 71% in the entire cohort (n=28) and 88% ORR and 75% CR in 16 patients treated at 25×106. With the median follow-up of 24 months, the 1-year EFS was 61% (95% CI: 45-82%). Overall, grade ≥3 CRS and ICANS rates were low at 4% and 7%. The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses and may benefit the treatment of other hematological malignancies, solid tumors and autoimmunity.

Authors
Jae Park, M Lia Palomba, Karlo Perica, Sean Devlin, Gunjan Shah, Parastoo Dahi, Richard Lin, Gilles Salles, Michael Scordo, Karthik Nath, Yannis Valtis, Alec 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, Faye Zhao, Jorge Mansilla Soto, Changhao He, Joel Meyerson, Kinga Hosszu, Devin Mcavoy, Xiuyan Wang, Isabelle Riviere, Michel Sadelain