Cargando…

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...

Descripción completa

Detalles Bibliográficos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Editorial office of Chinese Journal of Hematology 2022
Materias:
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
_version_ 1784739926136324096
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
work_keys_str_mv AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū
AT bǎxiàngcd33kàngyuánsāntèyìxìngtxìbāoxiánjiēqìdezhìbèijíduìbáixuèbìngxìbāodezuòyòngyánjiū