Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently

CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). CD19 relapse and the lack of CAR-T cell persistence which resul...

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Bibliographic Details
Published in:Science China. Life sciences 2023-04, Vol.66 (4), p.754-770
Main Authors: Chen, Zhaoqi, Liu, Yan, Chen, Nianci, Xing, Haiyan, Tian, Zheng, Tang, Kejing, Rao, Qing, Xu, Yingxi, Wang, Ying, Wang, Min, Wang, Jianxiang
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Animals
Antigens
Antigens, CD19
Antigens, CD20
Biomedical and Life Sciences
CD19 antigen
CD20 antigen
Chimeric antigen receptors
Chronic lymphocytic leukemia
Humans
Immunotherapy, Adoptive
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Life Sciences
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Lymphoma - therapy
Malignancy
Mice
Non-Hodgkin's lymphoma
Receptors, Chimeric Antigen
Research Paper
T-Lymphocytes
Tumor cell lines
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Summary:CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). CD19 relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome. CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape. Here, we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen. Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells, suggesting they exhibited dual antigen targeting of CD19 and CD20. By comparing the efficiency of four bispecific CAR modified T cells, it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’ primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model. These data highlighted the potential of loop2019 CAR-T in clinical treatment.
ISSN:1674-7305
1869-1889
DOI:10.1007/s11427-022-2173-9