Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia
Posted on 2020-05-19 - 03:55
Abstract Background Despite the impressive complete remission (CR) induced by CD19 CAR-T cell therapy in B-ALL, the high rate of complete responses is sometimes limited by the emergence of CD19-negative leukemia. Bispecific CAR-modified T cells targeting both CD19 and CD22 may overcome the limitation of CD19-negative relapse. Methods We here report the design of a bispecific CAR simultaneous targeting of CD19 and CD22. We performed a phase 1 trial of bispecific CAR T cell therapy in patients with relapsed/refractory precursor B-ALL at a dose that ranged from 1.7 × 106 to 3 × 106 CAR T cells per kilogram of body weight. Results We demonstrate bispecific CD19/CD22 CAR T cells could trigger robust cytolytic activity against target cells. MRD-negative CR was achieved in 6 out of 6 enrolled patients. Autologous CD19/CD22 CAR T cells proliferated in vivo and were detected in the blood, bone marrow, and cerebrospinal fluid. No neurotoxicity occurred in any of the 6 patients treated. Of note, one patient had a relapse with blast cells that no longer expressed CD19 and exhibited diminished CD22 site density approximately 5 months after treatment. Conclusion In brief, autologous CD19/CD22 CAR T cell therapy is feasible and safe and mediates potent anti-leukemic activity in patients with relapsed/refractory B-ALL. Furthermore, the emergence of target antigen loss and expression downregulation highlights the critical need to anticipate antigen escape. Our study demonstrates the reliability of bispecific CD19/CD22 CAR T cell therapy in inducing remission in adult patients with relapsed/refractory B-ALL. Trial registration ClinicalTrials.gov identifier: NCT03185494.
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Dai, Hanren; Wu, Zhiqiang; Jia, Hejin; Tong, Chuan; Guo, Yelei; Ti, Dongdong; et al. (2020). Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4925148.v2
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AUTHORS (15)
HD
Hanren Dai
ZW
Zhiqiang Wu
HJ
Hejin Jia
CT
Chuan Tong
YG
Yelei Guo
DT
Dongdong Ti
XH
Xiao Han
YL
Yang Liu
WZ
Wenying Zhang
CW
Chunmeng Wang
YZ
Yajing Zhang
MC
Meixia Chen
QY
Qingming Yang
YW
Yao Wang
WH
Weidong Han