TY - JOUR
T1 - Mechanisms underlying resistance to CAR-T cell therapy and strategies for enhancement
AU - Wu, Anran
AU - Zhang, Tingying
AU - Yu, Hongkai
AU - Cao, Yuyue
AU - Zhang, Rui
AU - Shao, Ruonan
AU - Liu, Bofeng
AU - Chen, Liting
AU - Xu, Kailin
AU - Chen, Wei
AU - Ho, Jinyuan
AU - Shi, Xiaofeng
N1 - Publisher Copyright:
© 2025 Elsevier Ltd
PY - 2025/6
Y1 - 2025/6
N2 - Chimeric antigen receptor (CAR) T-cell therapy has emerged as a revolutionary approach in the treatment of hematological malignancies, including acute lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma. Despite its promise, the clinical efficacy is often hampered by transient efficacy and subsequent relapse, which curtail the long-term success of this treatment. Current research focuses on overcoming these obstacles by exploring multitarget strategies and optimizing CAR-T cell design. This review summarizes recent insights into the resistance mechanisms associated with CAR-T cell therapy, and delineates emerging strategies for optimized CAR construction, including targeting multiple antigens, improving CAR design, and enhancing T-cell persistence. The goal is to provide a comprehensive overview of the field's current landscape to guide future research and the clinical application of CAR-T cell therapies.
AB - Chimeric antigen receptor (CAR) T-cell therapy has emerged as a revolutionary approach in the treatment of hematological malignancies, including acute lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma. Despite its promise, the clinical efficacy is often hampered by transient efficacy and subsequent relapse, which curtail the long-term success of this treatment. Current research focuses on overcoming these obstacles by exploring multitarget strategies and optimizing CAR-T cell design. This review summarizes recent insights into the resistance mechanisms associated with CAR-T cell therapy, and delineates emerging strategies for optimized CAR construction, including targeting multiple antigens, improving CAR design, and enhancing T-cell persistence. The goal is to provide a comprehensive overview of the field's current landscape to guide future research and the clinical application of CAR-T cell therapies.
KW - antigen escape
KW - CAR-T cell exhaustion
KW - cellular immunotherapy
KW - chimeric antigen receptor T-cell therapy
KW - drug resistance
UR - http://www.scopus.com/inward/record.url?scp=105004451599&partnerID=8YFLogxK
U2 - 10.1016/j.cytogfr.2025.04.002
DO - 10.1016/j.cytogfr.2025.04.002
M3 - Review article
C2 - 40340171
AN - SCOPUS:105004451599
SN - 1359-6101
VL - 83
SP - 66
EP - 76
JO - Cytokine and Growth Factor Reviews
JF - Cytokine and Growth Factor Reviews
ER -