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TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss

BACKGROUND: To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells. METHODS: TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T...

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Autores principales: Li, Guangchao, Zhang, Qing, Liu, Zhi, Shen, Huijuan, Zhu, Yangmin, Zhou, Zhao, Ding, Wen, Han, Siqi, Zhou, Jie, Ou, Ruiming, Luo, Min, Liu, Shuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052726/
https://www.ncbi.nlm.nih.gov/pubmed/33865370
http://dx.doi.org/10.1186/s12935-021-01923-x
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author Li, Guangchao
Zhang, Qing
Liu, Zhi
Shen, Huijuan
Zhu, Yangmin
Zhou, Zhao
Ding, Wen
Han, Siqi
Zhou, Jie
Ou, Ruiming
Luo, Min
Liu, Shuang
author_facet Li, Guangchao
Zhang, Qing
Liu, Zhi
Shen, Huijuan
Zhu, Yangmin
Zhou, Zhao
Ding, Wen
Han, Siqi
Zhou, Jie
Ou, Ruiming
Luo, Min
Liu, Shuang
author_sort Li, Guangchao
collection PubMed
description BACKGROUND: To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells. METHODS: TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T cells were intravenously injected into Raji-luciferase xenograft mice. CD19 antigens losing lymphoblasts was simulated by Raji knocking out CD19 (CD19(KO)) to investigate the effect of TriBAFF-CAR-T cells on CD19(KO) Raji. RESULTS: Both TriBAFF-CAR-T and CD19-CAR-T cells significantly induced the lysis of Raji, BALL-1, and Jeko-1. Moreover, when CD19-CAR-T cells specifically caused the lysis of K562 with overexpressed CD19, the lethal effect of TriBAFF-CAR-T cells was also specific for BAFFR-bearing K562 with increasing levels of interleukin-2 and INF-γ. The TriBAFF-CAR-T have the same effect with CD19-CAR-T cells in treating Raji xenofraft mice. TriBAFF-CAR-T cells also have great effect in CD19(KO) Raji cells. CONCLUSIONS: In this study, we successfully constructed novel TriBAFF-CAR-T cells to eliminate BAFFR-bearing and CD19 antigen loss in hematological tumor cells.
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spelling pubmed-80527262021-04-19 TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss Li, Guangchao Zhang, Qing Liu, Zhi Shen, Huijuan Zhu, Yangmin Zhou, Zhao Ding, Wen Han, Siqi Zhou, Jie Ou, Ruiming Luo, Min Liu, Shuang Cancer Cell Int Primary Research BACKGROUND: To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells. METHODS: TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T cells were intravenously injected into Raji-luciferase xenograft mice. CD19 antigens losing lymphoblasts was simulated by Raji knocking out CD19 (CD19(KO)) to investigate the effect of TriBAFF-CAR-T cells on CD19(KO) Raji. RESULTS: Both TriBAFF-CAR-T and CD19-CAR-T cells significantly induced the lysis of Raji, BALL-1, and Jeko-1. Moreover, when CD19-CAR-T cells specifically caused the lysis of K562 with overexpressed CD19, the lethal effect of TriBAFF-CAR-T cells was also specific for BAFFR-bearing K562 with increasing levels of interleukin-2 and INF-γ. The TriBAFF-CAR-T have the same effect with CD19-CAR-T cells in treating Raji xenofraft mice. TriBAFF-CAR-T cells also have great effect in CD19(KO) Raji cells. CONCLUSIONS: In this study, we successfully constructed novel TriBAFF-CAR-T cells to eliminate BAFFR-bearing and CD19 antigen loss in hematological tumor cells. BioMed Central 2021-04-17 /pmc/articles/PMC8052726/ /pubmed/33865370 http://dx.doi.org/10.1186/s12935-021-01923-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Li, Guangchao
Zhang, Qing
Liu, Zhi
Shen, Huijuan
Zhu, Yangmin
Zhou, Zhao
Ding, Wen
Han, Siqi
Zhou, Jie
Ou, Ruiming
Luo, Min
Liu, Shuang
TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss
title TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss
title_full TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss
title_fullStr TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss
title_full_unstemmed TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss
title_short TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss
title_sort tribaff-car-t cells eliminate b-cell malignancies with baffr-expression and cd19 antigen loss
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052726/
https://www.ncbi.nlm.nih.gov/pubmed/33865370
http://dx.doi.org/10.1186/s12935-021-01923-x
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