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靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究
OBJECTIVE: To investigate the effect of CD33-targeted bi-specific and tri-specific T-cell engagers on T-cell proliferation and explore their cytotoxicity on leukemia cells. METHODS: The CD33-targeted bi-specific T-cell engager(CD33-BiTE)and tri-specific T-cell engager(CD33-TriTE)expression vectors w...
Formato: | Online Artículo Texto |
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Lenguaje: | English |
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Editorial office of Chinese Journal of Hematology
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250957/ https://www.ncbi.nlm.nih.gov/pubmed/35680594 http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2022.05.005 |
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collection | PubMed |
description | OBJECTIVE: To investigate the effect of CD33-targeted bi-specific and tri-specific T-cell engagers on T-cell proliferation and explore their cytotoxicity on leukemia cells. METHODS: The CD33-targeted bi-specific T-cell engager(CD33-BiTE)and tri-specific T-cell engager(CD33-TriTE)expression vectors were successfully constructed and expressed through a eukaryotic cell expression system. CD33-BiTE and CD33-TriTE were purified by affinity chromatography. The effects of CD33-BiTE and CD33-TriTE on T cells were analyzed through in vitro experiments. RESULTS: ① CD33-BiTE and CD33-TriTE were successfully constructed and purified and could compete with flow cytometry antibodies for binding to the target cells. ② After 12 days of co-culture with CD33-BiTE and CD33-TriTE, the number of human T cells were expanded to 33.89±19.46 and 81.56±23.62 folds, respectively. CD33-TriTE induced a stronger proliferation of T cells than CD33-BiTE(P<0.05). ③ Both CD33-BiTE and CD33-TriTE induced specific dose-dependent cytotoxicity on CD33(+) leukemia cells. ④ Compared to CD33-TriTE, leukemia cells were prone to express PD-L1 when co-cultured with T cells and CD33-BiTE. CD33-TriTE induced powerful cytotoxicity on leukemia cells with high PD-L1 expression. CONCLUSION: CD33-BiTE and CD33-TriTE expression vectors were constructed, and fusion proteins were expressed in eukaryotic cells. Our results support the proliferative and activating effects of BiTE and TriTE on T cells. Compared to that of CD33-BiTE, CD33-TriTE induced a stronger proliferative effect on T cells and a more powerful cytotoxicity on leukemia cells with high PD-L1 expression. |
format | Online Article Text |
id | pubmed-9250957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Editorial office of Chinese Journal of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-92509572022-07-08 靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究 Zhonghua Xue Ye Xue Za Zhi 论著 OBJECTIVE: To investigate the effect of CD33-targeted bi-specific and tri-specific T-cell engagers on T-cell proliferation and explore their cytotoxicity on leukemia cells. METHODS: The CD33-targeted bi-specific T-cell engager(CD33-BiTE)and tri-specific T-cell engager(CD33-TriTE)expression vectors were successfully constructed and expressed through a eukaryotic cell expression system. CD33-BiTE and CD33-TriTE were purified by affinity chromatography. The effects of CD33-BiTE and CD33-TriTE on T cells were analyzed through in vitro experiments. RESULTS: ① CD33-BiTE and CD33-TriTE were successfully constructed and purified and could compete with flow cytometry antibodies for binding to the target cells. ② After 12 days of co-culture with CD33-BiTE and CD33-TriTE, the number of human T cells were expanded to 33.89±19.46 and 81.56±23.62 folds, respectively. CD33-TriTE induced a stronger proliferation of T cells than CD33-BiTE(P<0.05). ③ Both CD33-BiTE and CD33-TriTE induced specific dose-dependent cytotoxicity on CD33(+) leukemia cells. ④ Compared to CD33-TriTE, leukemia cells were prone to express PD-L1 when co-cultured with T cells and CD33-BiTE. CD33-TriTE induced powerful cytotoxicity on leukemia cells with high PD-L1 expression. CONCLUSION: CD33-BiTE and CD33-TriTE expression vectors were constructed, and fusion proteins were expressed in eukaryotic cells. Our results support the proliferative and activating effects of BiTE and TriTE on T cells. Compared to that of CD33-BiTE, CD33-TriTE induced a stronger proliferative effect on T cells and a more powerful cytotoxicity on leukemia cells with high PD-L1 expression. Editorial office of Chinese Journal of Hematology 2022-05 /pmc/articles/PMC9250957/ /pubmed/35680594 http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2022.05.005 Text en 2022年版权归中华医学会所有 https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 License. |
spellingShingle | 论著 靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究 |
title | 靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究 |
title_full | 靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究 |
title_fullStr | 靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究 |
title_full_unstemmed | 靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究 |
title_short | 靶向CD33抗原三特异性T细胞衔接器的制备及对白血病细胞的作用研究 |
title_sort | 靶向cd33抗原三特异性t细胞衔接器的制备及对白血病细胞的作用研究 |
topic | 论著 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250957/ https://www.ncbi.nlm.nih.gov/pubmed/35680594 http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2022.05.005 |
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