The preparation of VEGFR1/CD3 bispecific antibody and its specific cytotoxicity against VEGFR1-positive breast cancer cells

Bispecific antibody (BsAb) has been proved to be a very effective antitumor approach because of its distinctive advantages of immune‐mediated cytotoxicity. To enhance the ability to recruit and activate T lymphocytes for tumor‐specific killing, we constructed and prepared a recombinant human single‐...

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Bibliographic Details
Published in:Biotechnology and applied biochemistry 2014-07, Vol.61 (4), p.376-384
Main Authors: Tang, Ping, Li, Li, Zhou, Yan, Shen, Cong-Cong, Kang, Yu-Huan, Yao, Yu-Qin, Yi, Cheng, Gou, Lan-Tu, Yang, Jin-Liang
Format: Article
Language:English
Subjects:
Animals
Antibodies, Bispecific - biosynthesis
Antibodies, Bispecific - immunology
Antibodies, Bispecific - therapeutic use
antibody drug
Breast Neoplasms - drug therapy
Breast Neoplasms - immunology
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
CD3 Complex - immunology
Cell Line, Tumor
Cell Proliferation
CHO Cells
Cricetulus
Drug Screening Assays, Antitumor
Humans
immunotherapy
T lymphocyte
tumor
Vascular Endothelial Growth Factor Receptor-1 - immunology
VEGFR1/CD3 BsAb
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Summary:Bispecific antibody (BsAb) has been proved to be a very effective antitumor approach because of its distinctive advantages of immune‐mediated cytotoxicity. To enhance the ability to recruit and activate T lymphocytes for tumor‐specific killing, we constructed and prepared a recombinant human single‐chain Fv bispecific antibody (BsAb), named VEGFR1/CD3 BsAb, targeting VEGFR1 and CD3. The VEGFR1/CD3 BsAb was expressed in CHO‐K1 cells and purified by Ni‐NTA affinity chromatography. The CD3 and VEGFR1‐binding activity of VEGFR1/CD3 BsAb was confirmed by flow cytometry. T lymphocyte activation and proliferation induced by VEGFR1/CD3 BsAb were also demonstrated in vitro. Notably, our VEGFR1/CD3 BsAb presented a powerful and specific killing effect against VEGFR1‐positive human breast cancer cell MDA‐MB‐231 and MDA‐MB‐435 through activating T lymphocyte at very low concentrations, indicating that it will be a valuable antibody drug for treatment of VEGFR1‐positive cancers in the future.
ISSN:0885-4513
1470-8744
DOI:10.1002/bab.1187