Inhibition activity of a disulfide-stabilized diabody against basic fibroblast growth factor in lung cancer

Cai, Yaxiong; Yao, Shuange; Zhong, Jiangchuan; Zhang, Jinxia; Jiang, Haowu; Deng, Yanrui; Deng, Ning

doi:10.18632/oncotarget.15556

Cited by 9 publications

(11 citation statements)

References 23 publications

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“…Ligand traps, on the other hand, target soluble growth factors, and by sequestering them prevent activation of FGFRs on cancerous cells. This group is represented by natural FGFs binders, such as heparin, thrombospondin-1 (TSP-1), or longpentraxin-3 (PTX-3) [ 34 ], as well as soluble decoy FGFRs [ 17 , 35 ] and synthetic molecules able to bind FGFs, e.g., heparin-like polyanionic molecules [ 36 ] and anti-FGF1 antibodies [ 20 , 21 , 22 ]. To date, among the listed FGF traps, a promising molecule is FP-1039, a soluble FGFR1-Fc fusion protein that binds almost all FGFs, and thus inhibits growth of different tumor cell lines, including lung and endometrial cancer, as well as mesothelioma cell lines [ 35 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Among anti-FGF antibodies developed for therapeutic applications, FGF2 is the most commonly chosen target for selection of antibodies or antibody fragments [ 20 , 21 , 22 ], but there are also few reports on anti-FGF1 [ 24 , 38 ], anti-FGF8b [ 23 ], and anti-FGF23 [ 25 ]. Regarding antibodies binding FGF1, there is a scFv1C9 developed by the group of Xiao-Juan Zhu [ 24 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Ligand traps are based either on FGFR fragments acting as decoy molecules [ 16 , 17 ], peptides derived from natural FGF binders [ 18 , 19 ], or anti-FGF antibodies. Currently known anti-FGF antibodies have been developed mostly against FGF2, either generated in mice [ 20 ] or selected by screening libraries of formats such as scFv [ 21 ] and later reformatted to diabody [ 22 ]. Besides FGF2, mouse antibodies have been generated also against FGF1, FGF8b, and FGF23 and were shown to inhibit growth of breast and prostate cancer cells [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity

Chudzian

Szlachcic

Zakrzewska

et al. 2018

IJMS

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Fibroblast growth factor 1 (FGF1) and its receptors (FGFRs) regulate crucial biological processes such as cell proliferation and differentiation. Aberrant activation of FGFRs by their ligands can promote tumor growth and angiogenesis in many tumor types, including lung or breast cancer. The development of FGF1-targeting molecules with potential implications for the therapy of FGF1-driven tumors is recently being considered a promising approach in the treatment of cancer. In this study we have used phage display selection to find scFv antibody fragments selectively binding FGF1 and preventing it from binding to its receptor. Three identified scFv clones were expressed and characterized with regard to their binding to FGF1 and ability to interfere with FGF1-induced signaling cascades activation. In the next step the scFvs were cloned to scFv-Fc format, as dimeric Fc fusions prove beneficial in prospective therapeutic application. As expected, scFvs-Fc exhibited significantly increased affinity towards FGF1. We observed strong antiproliferative activity of the scFvs and scFvs-Fc in the in vitro cell models. Presented antibody fragments serve as novel FGF1 inhibitors and can be further utilized as powerful tools to use in the studies on the selective cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity

Chudzian

Szlachcic

Zakrzewska

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…When the absorptive values of positive clones/the absorptive values of negative ones ≥2.1, it was judged as a positive clone. After identification by phage-ELISA, the results showed that seven clones (8,9,15,25,26,28,30) were positive (Fig. 4C).…”

Section: Screening Of Anti-pd-l1 Fab Antibodymentioning

confidence: 99%

“…Antibody drugs play an important role in tumor therapy (Cai et al, 2017;Zhang et al, 2021). In 1986, the United States FDA approved the world's first monoclonal antibody OKT3 (mouse source) (Aksentijevich and Flinn, 2002).…”

Section: Introductionmentioning

confidence: 99%

Construction of a Natural Human Fab Phage Antibody Library and Screening of Phage Antibody against PD-L1

J¹,

Guo²,

Zhang³

et al. 2022

ijSciences

Self Cite

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Programmed Death Ligand-1(PD-L1) is an important target to drive T cell dysfunction when it connects with Programmed Death-1(PD-1), leading to immune escape of tumor cells, thus anti-PD-L1 antibody shows a promising prospect in the treatment of tumor. In order to construct a large natural antibody library, we collected a large number of lymphocytes of adults and children. The light chain and Fd genes of antibody were amplified by PCR, and the Fab phage antibody library with a library capacity of 4.27×10 9 was constructed. The insertion rates of the light chain library and the Fab library were 90% and 70%, respectively. The cloned sequences identified by PCR showed that all the sequences analyzed were unique, and the amino acid sequences of the CDR regions were diverse, which proved that there was good diversity in the antibody library. The positive clones that bind to PD-L1 were screened by phage ELISA, PCR identification and sequence analysis. In the end, two high-affinity positive clones were determined. The successful construction of this natural phage antibody library provided an effective method for screening human PD-L1 antibodies, which was expected to screen humanized antibodies against various antigens.

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Humanized disulfide‐stabilized diabody against fibroblast growth factor‐2 inhibits PD‐L1 expression and epithelial‐mesenchymal transition in hepatoma cells through STAT3

Sun,

Song,

et al. 2023

IUBMB Life

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Fibroblast growth factor 2 (FGF2) plays an important role in tumor angiogenesis. Humanized disulfide‐stable double‐chain antibody against fibroblast growth factor‐2 (anti‐FGF2 ds‐Diabody) is a small molecule antibody with good tissue permeability and low immunogenicity, which has potential in tumor‐targeted therapy. This study intended to investigate the effect of anti‐FGF2 ds‐Diabody on the migration and expression of programmed death‐ligand1 (PD‐L1) in hepatocellular carcinoma (HCC) cells. The anti‐FGF2 ds‐Diabody was expressed under methanol induction and purified with Ni2+‐affinity chromatography. Anti‐FGF2 ds‐Diabody significantly inhibited cell viability and proliferation in SK‐Hep1 and HepG2 cells as confirmed by CCK‐8 assays and colony formation assays. Western blot assays indicated that the proliferation of SK‐Hep1 and HepG2 cells was inhibited by anti‐FGF2 ds‐Diabody through inhibiting the phosphorylation activation of AKT and MAPK. The results of transwell and western blot assays showed that the migration and invasion of SK‐Hep1 and HepG2 cells were suppressed by anti‐FGF2 ds‐Diabody by affecting the epithelial‐mesenchymal transition (EMT) process. Meanwhile, anti‐FGF2 ds‐Diabody inhibited the expression of PD‐L1, and STAT3 participated in this process. Analysis of RT‐PCR and Western blot suggested that fibroblast growth factor receptor 4 inhibitor 1 (FGFR4‐IN‐1) suppressed the expression of PD‐L1, while STAT3 overexpression reversed this inhibitory effect. In addition, overexpression of STAT3 promoted migration and invasion and restored the suppressive effect of anti‐FGF2 ds‐Diabody on EMT. In conclusion, anti‐FGF2 ds‐Diabody could inhibit the expression of PD‐L1 and EMT of hepatoma cells through FGF2/FGFR4/STAT3 axis. These results suggested that anti‐FGF2 ds‐Diabody has potential clinical application in inhibiting metastasis and immune escape of hepatocellular carcinoma.

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Inhibition activity of a disulfide-stabilized diabody against basic fibroblast growth factor in lung cancer

Cited by 9 publications

References 23 publications

Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity

Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity

Construction of a Natural Human Fab Phage Antibody Library and Screening of Phage Antibody against PD-L1

Humanized disulfide‐stabilized diabody against fibroblast growth factor‐2 inhibits PD‐L1 expression and epithelial‐mesenchymal transition in hepatoma cells through STAT3

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