Development trends for generation of single-chain antibody fragments

Farajnia, Safar; Ahmadzadeh, Vahideh; Tanomand, Asghar; Veisi, Kamal; Khosroshahi, Shiva Ahdi; Rahbarnia, Leila

doi:10.3109/08923973.2014.945126

Cited by 51 publications

(25 citation statements)

References 150 publications

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“…Tumors in particular, where the blood supply is viscous and there is high interstitial fluid pressure, are difficult to penetrate [11,17]. This has been overcome to some extent by the use of antibody fragments, including scFv [12,20], which at approximately 27 kDa, are 5-fold smaller than IgG. The effectiveness of these fragments in cancer treatment is limited by the absence of the Fc domain, preventing antibodymediated cytotoxicity, but to compensate, the fragments can be conjugated to anti-cancer drugs [21].…”

Section: Current Limitations Of Therapeutic Mabsmentioning

confidence: 99%

Therapeutic Potential of Inorganic Nanoparticles for the Delivery of Monoclonal Antibodies

Turner

McInnes

Voelcker

et al. 2015

Journal of Nanomaterials

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Monoclonal antibodies (mAbs), available for a range of diseases, including tumours, leukemia, and multiple sclerosis, are emerging as the fastest growing area of therapeutic drug development. The greatest advantage of therapeutic mAbs is their ability to bind with a high degree of specificity to target proteins involved in disease pathophysiology. In response, effector functions are triggered and these ameliorate the disease cascade. As an alternative to this reliance on effector functions, drugs can be conjugated to mAbs. The ability to target compounds to the site of pathology minimises the nonspecific side effects associated with systemic administration. In both instances, optimising the delivery, absorption, and distribution of the mAbs, whilst minimising potential side effects, remain the key hurdles to improved clinical outcomes. Novel delivery strategies are being investigated with more vigour in recent years, and nanoparticles are being identified as suitable vehicles. In conjunction with permitting a controlled release profile, nanoparticles protect the drug from degradation, reducing both the dose and frequency of administration. Moreover, these particles shield the patient from the immune complications associated with high dose mAb infusions or drug cytotoxicity. This review outlines recent advances in nanoparticle technology and how they may be of benefit as therapeutic mAb delivery/targeting vehicles. StructureThe main type of therapeutic mAb is IgG, approximately 150 kDa sized Y-shaped protein structures comprised of two heavy chains linked by disulphide bridges to two light chains (Figure 1(a)). IgG antibodies contain two identical antigen binding sites (Fab), each containing complementarity determining regions (CDRs), which are variable in sequence. IgG antibodies also contain a conserved Fc domain which

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Section: Current Limitations Of Therapeutic Mabsmentioning

confidence: 99%

Therapeutic Potential of Inorganic Nanoparticles for the Delivery of Monoclonal Antibodies

Turner

McInnes

Voelcker

et al. 2015

Journal of Nanomaterials

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“…Protein therapeutics are becoming more and more prevalent in the treatment of a variety of diseases and medical conditions. 1,2 However, as proteins are relatively unstable and readily degraded, there is a need to develop alternative effective delivery systems. 3 These delivery systems need to protect the protein from degradation by proteases and hydrolytic conditions whilst also being completely biodegradable naturally in the body after implantation or injection.…”

Section: Introductionmentioning

confidence: 99%

Surface engineering of porous silicon to optimise therapeutic antibody loading and release

et al. 2015

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“…Single chain antibodies have several desirable advantages over monoclonal antibodies such as better penetration due to their smaller size, human origin, being easily made, and high affinity and specificity which made them attractive alternatives to monoclonal antibodies in cancer immunotherapy (18,(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Production of Specific Anti-EGFR Single Chain Antibodies: A Promising Strategy in the Immunotherapy of EGFR Expressing Tumor Tissues

2017

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Background: EGFR (Epidermal growth factor receptor) is overexpressed in a number of cancers and plays an important role in several phenomena such as aggressiveness of tumor, decreased survival of the patient, and resistance to treatments such as hormone therapy, chemotherapy, and also radiation. Objectives:The aim of this study is to produce specific human single-chain antibodies against EGFR and evaluate its specificity against the immunodominant epitope in order to offer a new and efficient way in the treatment of EGFR-expressing tumor tissues. Methods:A phage antibody display library of scFv (single chain fragment variable) was panned against an immunodominant epitope of EGFR. In order to select the specific clones, DNA fingerprinting was performed and the common patterns were differentiated. ELISA (Enzyme linked immunosorbent assay) was done to confirm the panning results and show the specificity of the selected clones.Results: Two specific clones with the frequencies of 55% and 30% were differentiated. The clones showed positive ELISA with the corresponding epitope while no positive reaction was observed for negative controls: unrelated peptide, M13KO7 (helper phage), unrelated scFv and no peptide. Conclusions:Immunotherapy against cancer has been a new treatment strategy in the recent years. Small and high affinity scFvs have had a crucial role in this regard. The specific human anti-EGFR scFvs that were selected in this study and reacted with the corresponding epitopehave the potential to be applied as a blocking antibody for interfering with tumor growth in EGFR-expressing tumors. Further studies are needed to evaluate the effects of these antibodies in vitro and in vivo.

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Development trends for generation of single-chain antibody fragments

Cited by 51 publications

References 150 publications

Therapeutic Potential of Inorganic Nanoparticles for the Delivery of Monoclonal Antibodies

Therapeutic Potential of Inorganic Nanoparticles for the Delivery of Monoclonal Antibodies

Surface engineering of porous silicon to optimise therapeutic antibody loading and release

Production of Specific Anti-EGFR Single Chain Antibodies: A Promising Strategy in the Immunotherapy of EGFR Expressing Tumor Tissues

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