Biomarker Research (May 2020)

Mechanisms underlying CD19-positive ALL relapse after anti-CD19 CAR T cell therapy and associated strategies

  • Yuru Nie,
  • Weiqing Lu,
  • Daiyu Chen,
  • Huilin Tu,
  • Zhenling Guo,
  • Xuan Zhou,
  • Meifang Li,
  • Sanfang Tu,
  • Yuhua Li

DOI
https://doi.org/10.1186/s40364-020-00197-1
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 17

Abstract

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Abstract Chimeric antigen receptor (CAR) T cell therapy, especially anti-CD19 CAR T cell therapy, has shown remarkable anticancer activity in patients with relapsed/refractory acute lymphoblastic leukemia, demonstrating an inspiring complete remission rate. However, with extension of the follow-up period, the limitations of this therapy have gradually emerged. Patients are at a high risk of early relapse after achieving complete remission. Although there are many studies with a primary focus on the mechanisms underlying CD19- relapse related to immune escape, early CD19+ relapse owing to poor in vivo persistence and impaired efficacy accounts for a larger proportion of the high relapse rate. However, the mechanisms underlying CD19+ relapse are still poorly understood. Herein, we discuss factors that could become obstacles to improved persistence and efficacy of CAR T cells during production, preinfusion processing, and in vivo interactions in detail. Furthermore, we propose potential strategies to overcome these barriers to achieve a reduced CD19+ relapse rate and produce prolonged survival in patients after CAR T cell therapy.

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