Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity.
Anti-CXCR4 Single-Chain Variable Fragment Antibodies Have Anti-Tumor Activity.
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DOI：
10.3389/fonc.2020.571194
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发表时间：
2020
影响因子：
4.7
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Liang GQ;Liu J;Zhou XX;Lin ZX;Chen T;Chen G;Wei H
单克隆抗体（mAb）是大的并且作为癌症治疗剂具有局限性。人源性单链抗体（scFv）是一种很好的小分子抗体替代物。它易于进入癌组织，无免疫原性，可在细菌中生产，降低成本。趋化因子受体CXCR4在不同的癌细胞中过表达。它在肿瘤的生长和转移中起重要作用。其过表达与癌症患者的不良预后相关，并被认为是癌症治疗的有吸引力的靶点。本研究以CXCR4胞外环2（ECL2）上的一个肽段为抗原，采用酵母双杂交方法筛选人源单链抗体库。分离三种抗CXCR4 scFv抗体。它们可以与CXCR 4蛋白和三种癌细胞系（DU 145、PC 3和MDA-MB-231）结合，而不与作为阴性对照的293T和3T3细胞结合。这三种单链抗体均能抑制肿瘤细胞的增殖、迁移和侵袭，并促进其凋亡。在小鼠异种移植模型中进一步检查两种scFv，并且它们抑制肿瘤生长。肿瘤免疫组化也表明，这两个scFv降低癌细胞增殖和肿瘤血管生成，并增加其凋亡。这些结果表明，这些抗CXCR4 scFv可以减少小鼠中的癌细胞增殖并抑制肿瘤生长，并且可以为各种癌症提供治疗。
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.
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影响因子：
5.7
作者：
Katsura M;Shoji F;Okamoto T;Shimamatsu S;Hirai F;Toyokawa G;Morodomi Y;Tagawa T;Oda Y;Maehara Y
通讯作者：
Maehara Y
影响因子：
11.5
作者：
Ghobrial, Irene M.;Liu, Chia-Jen;Becker, Pamela S.
通讯作者：
Becker, Pamela S.
DOI：
10.1016/j.jsbmb.2019.105406
发表时间：
2019-09-01
影响因子：
4.1
作者：
Jang, Yin-Gi;Go, Ryu-Eun;Choi, Kyung-Chul
通讯作者：
Choi, Kyung-Chul
影响因子：
--
作者：
Li, Yao-ping;Pang, Jing;Cui, Yongping
通讯作者：
Cui, Yongping
影响因子：
5.6
作者：
Liu, Yan;Ren, Chen-Chen;Chen, Yan-Nan
通讯作者：
Chen, Yan-Nan