Isolation of high-affinity, neutralizing anti-idiotype antibodies by phage and ribosome display for application in immunogenicity and pharmacokinetic analyses

Chin, Stacey E.; Ferraro, Franco; Groves, Maria; Liang, Meina; Vaughan, Tristan J.; Dobson, Claire

doi:10.1016/j.jim.2014.10.013

Cited by 17 publications

(16 citation statements)

References 28 publications

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“…provides the key to a wide spectrum of applications, including drug development, genetic engineering, biochemistry, biotechnology, molecular biology, etc 123456…”

mentioning

confidence: 99%

Continuous microfluidic assortment of interactive ligands (CMAIL)

Hsiao

Huang

et al. 2016

Sci Rep

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Finding an interactive ligand-receptor pair is crucial to many applications, including the development of monoclonal antibodies. Biopanning, a commonly used technique for affinity screening, involves a series of washing steps and is lengthy and tedious. Here we present an approach termed continuous microfluidic assortment of interactive ligands, or CMAIL, for the screening and sorting of antigen-binding single-chain variable antibody fragments (scFv) displayed on bacteriophages (phages). Phages carrying native negative charges on their coat proteins were electrophoresed through a hydrogel matrix functionalized with target antigens under two alternating orthogonal electric fields. During the weak horizontal electric field phase, phages were differentially swept laterally depending on their affinity for the antigen, and all phages were electrophoresed down to be collected during the strong vertical electric field phase. Phages of different affinity were spatially separated, allowing the continuous operation. More than 105 CFU (colony forming unit) antigen-interacting phages were isolated with ~100% specificity from a phage library containing 3 × 109 individual members within 40 minutes of sorting using CMAIL. CMAIL is rapid, sensitive, specific, and does not employ washing, elution or magnetic beads. In conclusion, we have developed an efficient and cost-effective method for isolating and sorting affinity reagents involving phage display.

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“…provides the key to a wide spectrum of applications, including drug development, genetic engineering, biochemistry, biotechnology, molecular biology, etc 123456…”

mentioning

confidence: 99%

Continuous microfluidic assortment of interactive ligands (CMAIL)

Hsiao

Huang

et al. 2016

Sci Rep

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“…Such antibody reagents have been made by animal immunization and by in vitro library methods. 7,8 Monoclonal anti-idiotypic antibodies can either bind to the drug antibody paratope, competing with drug target binding (named Type 1 in this study), or they bind the drug outside the paratope independent of the presence of target (Type 2). Type 1 reagents detect free drug, whereas Type 2 can bind to both the free and the bound form of the drug and therefore detect total drug levels.…”

Section: Discussionmentioning

confidence: 99%

“…Such reagents have been developed by animal immunizations and by in vitro methods such as phage display of antibody libraries. [6][7][8][9] PK assays making use of such reagents are typically built using the bridging assay format, taking advantage of the two binding sites of the antibody drugthe therapeutic antibody is captured from serum with an anti-idiotypic antibody binding to one binding site, and detection is performed with a second labeled anti-idiotypic antibody that binds to the second binding site. 10 Bridging assays require a low coating density of the capture reagent to avoid the therapeutic antibody binding to the surface with both arms, which would reduce the sensitivity of the assay.…”

Section: Introductionmentioning

confidence: 99%

Generation by phage display and characterization of drug-target complex-specific antibodies for pharmacokinetic analysis of biotherapeutics

Harth

Haaf

Loew

et al. 2018

mAbs

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Anti-idiotypic antibodies play an important role in pre-clinical and clinical development of therapeutic antibodies, where they are used for pharmacokinetic studies and for the development of immunogenicity assays. By using an antibody phage display library in combination with guided in vitro selection against various marketed drugs, we generated antibodies that recognize the drug only when bound to its target. We have named such specificities Type 3, to distinguish them from the anti-idiotypic antibodies that specifically detect free antibody drug or total drug. We describe the generation and characterization of such reagents for the development of ligand binding assays for drug quantification. We also show how these Type 3 antibodies can be used to develop very specific and sensitive assays that avoid the bridging format.Abbreviations: BAP: bacterial alkaline phosphatase; CDR: complementarity-determining regions in VH or VL; Fab: antigen-binding fragment of an antibody; HRP: horseradish peroxidase; HuCAL®: Human Combinatorial Antibody Libraries; IgG: immunoglobulin G; LBA: ligand binding assay; LOQ: limit of quantitation; NHS: normal human serum; PK: pharmacokinetics; VH: variable region of the heavy chain of an antibody; VL: variable region of the light chain of an antibody.

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“…The field of antibody affinity maturation represents the most successful application of ribosome display [ 46 , 50 , 51 , 52 , 53 , 54 ]. This display system, with its built-in affinity maturation feature caused by the error-prone DNA shuffling or site-directed mutagenesis process of reverse transcriptase and amplification, enables efficient maturation of picomolar antibody concentrations [ 20 , 27 , 52 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. With ribosome display systems employing such strategies, improvements greater than 1000-fold in potency within 6 months have been achieved for antibodies derived from phage display or from immunized animals [ 63 ].…”

Section: In Vitro Ribosome Displaymentioning

confidence: 99%

Ribosome Display Technology: Applications in Disease Diagnosis and Control

et al. 2020

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Antibody ribosome display remains one of the most successful in vitro selection technologies for antibodies fifteen years after it was developed. The unique possibility of direct generation of whole proteins, particularly single-chain antibody fragments (scFvs), has facilitated the establishment of this technology as one of the foremost antibody production methods. Ribosome display has become a vital tool for efficient and low-cost production of antibodies for diagnostics due to its advantageous ability to screen large libraries and generate binders of high affinity. The remarkable flexibility of this method enables its applicability to various platforms. This review focuses on the applications of ribosome display technology in biomedical and agricultural fields in the generation of recombinant scFvs for disease diagnostics and control.

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Isolation of high-affinity, neutralizing anti-idiotype antibodies by phage and ribosome display for application in immunogenicity and pharmacokinetic analyses

Cited by 17 publications

References 28 publications

Continuous microfluidic assortment of interactive ligands (CMAIL)

Continuous microfluidic assortment of interactive ligands (CMAIL)

Generation by phage display and characterization of drug-target complex-specific antibodies for pharmacokinetic analysis of biotherapeutics

Ribosome Display Technology: Applications in Disease Diagnosis and Control

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