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

Biomarker Research
Yuru NieYuhua Li

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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Citations

Sep 19, 2020·Journal of Hematology & Oncology·Bo YuDelong Liu
Apr 22, 2021·Journal of Hematology & Oncology·Jing-Zhou HouDelong Liu
Jul 3, 2021·International Journal of Molecular Sciences·Álvaro Martínez-RubioMaría Rosa
Aug 2, 2021·Biomarker Research·Hongtao LiuLei Zheng
Sep 29, 2021·Journal of Hematology & Oncology·Shaoming ZhuChong-Xian Pan
Sep 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samanta Romina ZanettiPablo Menéndez

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Methods Mentioned

BETA
transfection
transgenic
lymphodepletion

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