T cells redirected against Igβ for the immunotherapy of B cell lymphoma

CD19-redirected CAR-T immunotherapy has emerged as a promising strategy for treatment of B cell lymphoma, however, many patients often relapsed due to antigen loss. Therefore, it is urgently needed to explore other suitable antigens targeted by CAR-T cells to cure B cell lymphoma. Igβ is a component...

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Published in:Leukemia 2020-03, Vol.34 (3), p.821-830
Main Authors: Jiang, Dongpeng, Tian, Xiaopeng, Bian, Xiaosen, Zhu, Tingting, Qin, Huimin, Zhang, Ruixi, Xu, Yang, Pan, Zhansheng, Huang, Haiwen, Fu, Jianhong, Wu, Depei, Chu, Jianhong
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Language:English
Subjects:
13/31
14/34
14/5
42/41
64/60
692/699/1541/1990/291/1621/1915
692/699/67/1059/2325
96/44
Animals
Antigens
B-cell lymphoma
B-cell receptor
Cancer Research
Caspase-9
CD19 antigen
CD28 antigen
CD28 Antigens - metabolism
CD79 Antigens - immunology
Cell Line, Tumor
Coculture Techniques
Critical Care Medicine
Hematology
Humans
Immunotherapy
Immunotherapy, Adoptive
Intensive
Interferon
Internal Medicine
K562 Cells
Lymphocytes
Lymphocytes T
Lymphoma
Lymphoma, B-Cell - immunology
Lymphoma, B-Cell - therapy
Lysosomal-Associated Membrane Protein 1 - metabolism
Medicine
Medicine & Public Health
Mice
Mice, Inbred NOD
Mice, SCID
Mutation
Neoplasm Transplantation
Oncology
Receptors, Chimeric Antigen - immunology
Signal transduction
Suicide
Suicide genes
T-Lymphocytes - immunology
Xenografts
Xenotransplantation
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Fu, Jianhong
Wu, Depei
Chu, Jianhong
description CD19-redirected CAR-T immunotherapy has emerged as a promising strategy for treatment of B cell lymphoma, however, many patients often relapsed due to antigen loss. Therefore, it is urgently needed to explore other suitable antigens targeted by CAR-T cells to cure B cell lymphoma. Igβ is a component of the B cell receptor (BCR) complex, which is highly expressed on the surface of lymphoma cells. In this study, we engineered T cells to express anti-Igβ CAR with CD28 costimulatory signaling moiety and observed that Igβ-CAR T cells could efficiently recognize and eliminate Igβ + lymphoma cells both in vitro and in two different lymphoma xenograft models. The specificity of Igβ-CAR T cells was further confirmed through wild type or mutated Igβ gene transduction together with Igβ-specific knockout in target cells. Of note, both the in vitro and in vivo effect of Igβ CAR-T cells was comparable with that of CD19 CAR-T cells. Importantly, Igβ CAR-T cells recognized and eradicated patient-derived lymphoma cells in the autologous setting. Lastly, the safety of anti-Igβ CAR-T cells could be further enhanced by introduction of the inducible caspase-9 suicide gene system. Collectively, Igβ-specific CAR-T cells may be a promising immunotherapeutic approach for B cell lymphoma.
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subjects 13/31
14/34
14/5
42/41
64/60
692/699/1541/1990/291/1621/1915
692/699/67/1059/2325
96/44
Animals
Antigens
B-cell lymphoma
B-cell receptor
Cancer Research
Caspase-9
CD19 antigen
CD28 antigen
CD28 Antigens - metabolism
CD79 Antigens - immunology
Cell Line, Tumor
Coculture Techniques
Critical Care Medicine
Hematology
Humans
Immunotherapy
Immunotherapy, Adoptive
Intensive
Interferon
Internal Medicine
K562 Cells
Lymphocytes
Lymphocytes T
Lymphoma
Lymphoma, B-Cell - immunology
Lymphoma, B-Cell - therapy
Lysosomal-Associated Membrane Protein 1 - metabolism
Medicine
Medicine & Public Health
Mice
Mice, Inbred NOD
Mice, SCID
Mutation
Neoplasm Transplantation
Oncology
Receptors, Chimeric Antigen - immunology
Signal transduction
Suicide
Suicide genes
T-Lymphocytes - immunology
Xenografts
Xenotransplantation
title T cells redirected against Igβ for the immunotherapy of B cell lymphoma
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