Recombinant Antibody Fragments for Neurodegenerative Diseases

Manoutcharian, Karen; Perez-Garmendia, Roxanna; Gevorkian, Goar

doi:10.2174/1570159x01666160930121647

Cited by 37 publications

(21 citation statements)

References 148 publications

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“…in our previous study, a fully human display library was screened for anti-TSLP-scFv-Fc-84 that had high specificity and the capacity to block the TSlPr in vitro (25). However, single-chain antibodies screened from natural antibody libraries have low affinity and require affinity improvement (5). random mutation of gene fragments encoding variable regions and directed introduction of mutations are the primary methods for increasing the affinity of recombinant antibodies (26).…”

Section: Discussionmentioning

confidence: 99%

“…In general, scFv have a low stability, low affinity and a short half-life in vivo (5). Therefore, the pre-mutated scFv-84 and affinity enhanced scFv-M4 genes were inserted into the eukaryotic expression vector pcdna3.1-sp-Fc.…”

Section: Construction Of the Anti-tslp-scfv-fc Eukaryotic Expression mentioning

confidence: 99%

“…However, a fully human antibody reactive with TSlP is currently unavailable for clinical use. engineered antibodies have many advantages over murine monoclonal antibodies, including that they are not murine, and can be modified at the genetic and molecular levels to meet requirements for immunogenicity, stability and specificity in vivo (5). However, engineered antibodies obtained by antibody library screening have not undergone affinity maturation in vivo and their affinity is generally not acceptable for clinical use (6).…”

Section: Introductionmentioning

confidence: 99%

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Affinity improvement of the fully human anti‑TSLP recombinant antibody

Chen

Xian

et al. 2019

Mol Med Report

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Thymic stromal lymphopoietin (TSlP) is a potentially important target for the treatment of asthma and malignancies. However, a fully human antibody reactive with TSlP is currently unavailable for clinical use. in a previous study, a human anti-TSlP-single-chain antibody variable fragment (anti-TSlP-scFv) 84 was selected by phage display from a constructed human scFv library. in the present study, a computer simulation method was developed using Discovery Studio 4.5 software, to increase the affinity of anti-TSLP-scFv-84. Specific primers were designed and mutated dna sequences of anti-TSlP-scFvs were obtained by overlap extension Pcr. The mutant scFvs were expressed in plZ16 and affinity-enhanced anti-TSlP-scFv-M4 was screened using eliSa. However, in general the scFvs have low stability and short half-lives in vivo. Therefore, scFv-84 and scFv-M4 were inserted into eukaryotic expression vectors (pcdna3.1-sp-Fc and PMH3 en -sp-Fc) and then transfected into 293F cells to express anti-TSlP-scFv-Fc. eliSa and western blotting results indicated the size of the anti-TSlP-scFv-Fc to be ~50 kda. Binding of anti-TSlP-scFv-Fc-M4 to TSlP was enhanced compared with the pre-mutated scFv-Fc-84. The affinity of the mutated recombinant antibody was determined using the Biacore technique and found to be ~10-fold greater than the pre-mutated antibody.

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Section: Discussionmentioning

confidence: 99%

Section: Construction Of the Anti-tslp-scfv-fc Eukaryotic Expression mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Affinity improvement of the fully human anti‑TSLP recombinant antibody

Chen

Xian

et al. 2019

Mol Med Report

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“…Cancer. Several scFvs have been identified and tested in preclinical studies to target and treat many different pathologies encompassing autoimmune [121], neurological [122], and oncological diseases [123]. A number of studies have been carried out to isolate scFvs capable of specifically targeting signature proteins of a particular cancer cell, mainly exploiting the phage display technology [124].…”

Section: Scfv To Targetmentioning

confidence: 99%

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Baboci

Capolla

Cintio

et al. 2020

Journal of Oncology

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e development of nanostructures for therapeutic purpose is rapidly growing, following the results obtained in vivo in animal models and in the clinical trials. Unfortunately, the potential therapeutic efficacy is not completely exploited, yet. is is mainly due to the fast clearance of the nanostructures in the body. Nanoparticles and the liver have a unique interaction because the liver represents one of the major barriers for drug delivery. is interaction becomes even more relevant and complex when the drug delivery strategies employing nanostructures are proposed for the therapy of liver diseases, such as hepatocellular carcinoma (HCC). In this case, the selective delivery of therapeutic nanoparticles to the tumor microenvironment collides with the tendency of nanostructures to be quickly eliminated by the organ. e design of a new therapeutic approach based on nanoparticles to treat HCC has to particularly take into consideration passive and active mechanisms to avoid or delay liver elimination and to specifically address cancer cells or the cancer microenvironment. is review will analyze the different aspects concerning the dual role of the liver, both as an organ carrying out a clearance activity for the nanostructures and as target for therapeutic strategies for HCC treatment.

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“…An alternative approach is the expression of single-chain antibodies (scFvs) against Aβ from AAV in APP transgenic mice. scFv are truncation variants of IgGs comprising the variable, antigen recognizing regions of the IgG heavy, and light chains coupled by a linker sequence (Manoutcharian, Perez-Garmendia, & Gevorkian, 2017). scFvs retain the ability to bind the antigen but lack antigen cross-linking and T cell receptor activation properties.…”

Section: Gene Therapy Strategies In Ad Mouse Modelsmentioning

confidence: 99%

Adeno‐associated virus‐based Alzheimer's disease mouse models and potential new therapeutic avenues

Ittner

Klugmann

2019

British J Pharmacology

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Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that presents with cognitive decline. The current understanding of underlying disease mechanisms remains incomplete. Genetically modified mouse models have been instrumental in deciphering pathomechanisms in AD. While these models were typically generated by classical transgenesis and genome editing, the use of adeno‐associated viruses (AAVs) to model and investigate AD in mice, as well as to develop novel gene‐therapy approaches, is emerging. Here, we reviewed literature that used AAVs to study and model AD and discuss potential gene therapy strategies. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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Recombinant Antibody Fragments for Neurodegenerative Diseases

Cited by 37 publications

References 148 publications

Affinity improvement of the fully human anti‑TSLP recombinant antibody

Affinity improvement of the fully human anti‑TSLP recombinant antibody

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Adeno‐associated virus‐based Alzheimer's disease mouse models and potential new therapeutic avenues

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