Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity
Monoclonal antibodies (mAbs) are large and have limitations as cancer therapeutics. Human single-chain variable fragment (scFv) is a small antibody as a good alternative. It can easily enter cancer tissues, has no immunogenicity and can be produced in bacteria to decrease the cost. The chemokine rec...
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| Format: | Article |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.571194/full |
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| author | Guang-Quan Liang Jing Liu Xiao-Xin Zhou Ze-Xiong Lin Tao Chen Guo Chen Henry Wei |
| author_facet | Guang-Quan Liang Jing Liu Xiao-Xin Zhou Ze-Xiong Lin Tao Chen Guo Chen Henry Wei |
| author_sort | Guang-Quan Liang |
| collection | DOAJ |
| description | Monoclonal antibodies (mAbs) are large and have limitations as cancer therapeutics. Human single-chain variable fragment (scFv) is a small antibody as a good alternative. It can easily enter cancer tissues, has no immunogenicity and can be produced in bacteria to decrease the cost. The chemokine receptor CXCR4 is overexpressed in different cancer cells. It plays an important role in tumor growth and metastasis. Its overexpression is associated with poor prognosis in cancer patients and is regarded as an attractive target for cancer treatment. In this study, a peptide on the CXCR4 extracellular loop 2 (ECL2) was used as an antigen for screening a human scFv antibody library by yeast two-hybrid method. Three anti-CXCR4 scFv antibodies were isolated. They could bind to CXCR4 protein and three cancer cell lines (DU145, PC3, and MDA-MB-231) and not to 293T and 3T3 cells as negative controls. These three scFvs could decrease the proliferation, migration, and invasion of these cancer cells and promote their apoptosis. The two scFvs were further examined in a mouse xenograft model, and they inhibited the tumor growth. Tumor immunohistochemistry also demonstrated that the two scFvs decreased cancer cell proliferation and tumor angiogenesis and increased their apoptosis. These results show that these anti-CXCR4 scFvs can decrease cancer cell proliferation and inhibit tumor growth in mice, and may provide therapy for various cancers. |
| first_indexed | 2024-12-19T06:07:23Z |
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| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T06:07:23Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-2d91a21b1d5e4024be2b528398e454b52022-12-21T20:33:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-12-011010.3389/fonc.2020.571194571194Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor ActivityGuang-Quan Liang0Jing Liu1Xiao-Xin Zhou2Ze-Xiong Lin3Tao Chen4Guo Chen5Henry Wei6Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology and Institute of Biomedicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology and Institute of Biomedicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology and Institute of Biomedicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology and Institute of Biomedicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Cell Biology and Institute of Biomedicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaMonoclonal antibodies (mAbs) are large and have limitations as cancer therapeutics. Human single-chain variable fragment (scFv) is a small antibody as a good alternative. It can easily enter cancer tissues, has no immunogenicity and can be produced in bacteria to decrease the cost. The chemokine receptor CXCR4 is overexpressed in different cancer cells. It plays an important role in tumor growth and metastasis. Its overexpression is associated with poor prognosis in cancer patients and is regarded as an attractive target for cancer treatment. In this study, a peptide on the CXCR4 extracellular loop 2 (ECL2) was used as an antigen for screening a human scFv antibody library by yeast two-hybrid method. Three anti-CXCR4 scFv antibodies were isolated. They could bind to CXCR4 protein and three cancer cell lines (DU145, PC3, and MDA-MB-231) and not to 293T and 3T3 cells as negative controls. These three scFvs could decrease the proliferation, migration, and invasion of these cancer cells and promote their apoptosis. The two scFvs were further examined in a mouse xenograft model, and they inhibited the tumor growth. Tumor immunohistochemistry also demonstrated that the two scFvs decreased cancer cell proliferation and tumor angiogenesis and increased their apoptosis. These results show that these anti-CXCR4 scFvs can decrease cancer cell proliferation and inhibit tumor growth in mice, and may provide therapy for various cancers.https://www.frontiersin.org/articles/10.3389/fonc.2020.571194/fullCXCR4scFvcancerantibodyyeast two-hybrid |
| spellingShingle | Guang-Quan Liang Jing Liu Xiao-Xin Zhou Ze-Xiong Lin Tao Chen Guo Chen Henry Wei Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity Frontiers in Oncology CXCR4 scFv cancer antibody yeast two-hybrid |
| title | Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity |
| title_full | Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity |
| title_fullStr | Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity |
| title_full_unstemmed | Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity |
| title_short | Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity |
| title_sort | anti cxcr4 single chain variable fragment antibodies have anti tumor activity |
| topic | CXCR4 scFv cancer antibody yeast two-hybrid |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.571194/full |
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