Developing and characterization of single chain variable fragment (scFv) antibody against frizzled 7 (Fzd7) receptor

Nickho, Hamid; Younesi, Vahid; Aghebati‐Maleki, Leili; Motallebnezhad, Morteza; Zolbanin, Jafar Majidi; Pour, Aliakbar Movassagh; Yousefi, Mehdi

doi:10.1080/21655979.2016.1255383

Cited by 21 publications

(14 citation statements)

References 47 publications

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“…Functionally, the scFvs inhibited cell growth by inducing cell apoptosis in a TNBC cell line, MDA-MB-231. The reasons why scFvs antibodies are potential therapeutic agents include small size, high affinity, human origin, and specificity [ 89 , 90 ].…”

Section: Therapeutic Potential Of Fzd Receptorsmentioning

confidence: 99%

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Zeng

Chen

2018

IJMS

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Frizzled receptors (FZDs) are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs) that serve as receptors for secreted Wingless-type (WNT) ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

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Section: Therapeutic Potential Of Fzd Receptorsmentioning

confidence: 99%

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Zeng

Chen

2018

IJMS

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“…Genetic or pharmacological inhibition of elements of the Wnt/Fzd pathway (Fzd4, LRP-5, Dishevelled, and β-catenin) impairs retinal NV and vascular permeability. [24][25][26] Recent studies have demonstrated that the anti-Fzd7 antibody [27][28][29][30] antagonized Wnt/β-catenin signaling in Fzd7-expressing cancer cells, and suppressed tumor progression and metastasis. 21,22 Dysregulation of Wnt signaling is also associated with ocular diseases with an emphasis on DR. 23 Previously, we have demonstrated that Frizzled-7 (Fzd7) signaling controls post natal vessel formation in the retina, 20 however its role in pathological angiogenesis is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Therapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model

et al. 2019

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Retinopathies remain major causes of visual impairment in diabetic patients and premature infants. Introduction of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) has transformed therapy for these proliferative retinopathies.However, limitations associated with anti-VEGF medications require to unravel new pathways of vessel growth to identify potential drug targets. Here, we investigated the role of Wnt/Frizzled-7 (Fzd7) pathway in a mouse model of oxygen-induced retinopathy (OIR). Using transgenic mice, which enabled endothelium-specific and time-specific Fzd7 deletion, we demonstrated that Fzd7 controls both vaso-obliteration and neovascular phases (NV). Deletion of Fzd7 at P12, after the ischemic phase of OIR, prevented formation of aberrant neovessels into the vitreous by suppressing proliferation of endothelial cells (EC) in tufts. Next we validated in vitro two Frd7 blocking strategies: a monoclonal antibody (mAbFzd7) against Fzd7 and a soluble Fzd7 receptor (CRD). In vivo a single intravitreal microinjection of mAb-Fzd7 or CRD significantly attenuated retinal neovascularization (NV) in mice with OIR. Molecular analysis revealed that Fzd7 may act through the activation of Wnt/βcatenin and Jagged1 expression to control EC proliferation in extra-retinal neovessels. We identified Fzd7/β-catenin signaling as new regulator of pathological retinal NV. Fzd7 appears to be a potent pharmacological target to prevent or treat aberrant angiogenesis of ischemic retinopathies. K E Y W O R D S

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“…[22][23][24][25] Synergistically, Inppl1, Fzd7, and Tgf-b1 were activated as suppressors of cytokine signaling. [26][27][28] Gzmb and Tgf-b1 were confirmed by RT-PCR. A precious signal showed that intravaginal TGF-b can prevent spontaneous abortion in this model despite the recruitment of CD4 þ 8 þ FOXP3 þ cells.…”

Section: Discussionmentioning

confidence: 82%

Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

Zhang

Liu

et al. 2019

Reprod. Sci.

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The adverse clinical result and poor treatment outcome in recurrent spontaneous abortion (RSA) make it necessary to understand the pathogenic mechanism. The mating combination CBA/J × DBA/2 has been widely used as an abortion-prone model compared to DBA/2-mated CBA/J mice. Here, we used RNA-seq to get a comprehensive catalogue of genes differentially expressed between survival placenta in abortion-prone model and control. Five hundred twenty-four differentially expressed genes were obtained followed by clustering analysis, Gene Ontology analysis, and pathway analysis. We paid more attention to immune-related genes namely “immune response” and “immune system process” including 33 downregulated genes and 28 upregulated genes. Twenty-one genes contribute to suppressing immune system and 7 are against it. Six genes were validated by reverse transcription-polymerase chain reaction, namely Ccr1l1, Tlr4, Tgf-β1, Tyro3, Gzmb, and Il-1β. Furthermore, Tlr4, Tgf-β1, and Il-1β were analyzed by Western blot. Such immune profile gives us a better understanding of the complicated immune processing in RSA and immunosuppression can rescue pregnancy loss.

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Developing and characterization of single chain variable fragment (scFv) antibody against frizzled 7 (Fzd7) receptor

Cited by 21 publications

References 47 publications

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Therapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model

Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

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