Isolation and Characterization of a Monobody with a Fibronectin Domain III Scaffold That Specifically Binds EphA2

Park, Seung-Hwan; Park, Sukho; Kim, Dong Yeon; Pyo, Ayoung; Kimura, Richard H.; Sathirachinda, Ataya; Choy, Hyon E.; Min, Jung‐Joon; Gambhir, Sanjiv S.; Hong, Yeongjin

doi:10.1371/journal.pone.0132976

Cited by 24 publications

(29 citation statements)

References 44 publications

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“…To date, only two monobodies (E1 and E10) that specifically bind EphA2 have been developed and tested for prostate cancer cells. In vivo optical imaging showed strong targeting of Cy5.5-labeled E1 to mouse tumor tissue induced by PC3 human prostate cancer cell line that expresses a high level of hEphA2 [106].…”

Section: Minibodies Diabodies Single-chain Variable Region Fragmentmentioning

confidence: 99%

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

et al. 2020

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Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related deaths in Western civilization. Although localized prostate cancer can be treated effectively in different ways, almost all patients progress to the incurable metastatic castration-resistant prostate cancer. Due to the significant mortality and morbidity rate associated with the progression of this disease, there is an urgent need for new and targeted treatments. In this review, we summarize the recent advances in research on identification of prostate tissue-specific antigens for targeted therapy, generation of highly specific and selective molecules targeting these antigens, availability of therapeutic radionuclides for widespread medical applications, and recent achievements in the development of new-generation small-molecule inhibitors and antibody-based strategies for targeted prostate cancer therapy with alpha-, beta-, and Auger electron-emitting radionuclides.

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Section: Minibodies Diabodies Single-chain Variable Region Fragmentmentioning

confidence: 99%

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

et al. 2020

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“…In previous work from our group, a hEphA2-specific E1 monobody (<2 nM Kd) was isolated by screening a yeast surface display library [33]. E1 binds to human tumor cells and xenograft tumor tissues expressing high levels of hEphA2 on their cell surfaces.…”

Section: Introductionmentioning

confidence: 99%

Engineering of monobody conjugates for human EphA2-specific optical imaging

et al. 2017

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In a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E. coli. E1-Rluc8 and E1-EGFP specifically bound to hEphA2 in human prostate cancer PC3 cells but not in human cervical cancer HeLa cells, which express hEphA2 at high and low levels, respectively. These recombinant proteins maintained >40% activity in mouse serum at 24 h. In vivo optical imaging for 24 h did not detect E1-EGFP signals, whereas E1-Rluc8 showed tumor-specific luminescence signals in PC3 but not in HeLa xenograft mice. E1-Rluc8 signals were detected at 4 h, peaked at 12 h, and were undetectable at 24 h. These results suggest the potential of E1-Rluc8 as an EphA2-specific optical imaging agent.

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“…For the purpose of tumor imaging, another example of generating a high-affinity monobody is the E1h monobody that binds to the membrane-bound hepatocellular receptor tyrosine kinase class A2 (EphA2), which is highly expressed in several types of cancers, including those of the lung, prostate, breast, and colon. In the study, E1h conjugated with NIR fluorescent dye Cy5.5 showed tumor targeting and imaging in a murine model of prostate cancer (102) (Figure 6 b ). …”

Section: Antibody Mimeticsmentioning

confidence: 94%

“…Nude mice were pretreated with nontagged E1h (+) or without (−). Panel reproduced with permission from Reference 102 under the terms of the Creative Commons Attribution 4.0 International license, http://creativecommons.org/licenses/by/4.0. Abbreviations: KD, knockdown; MEF, mouse embryonic fibroblast; PBS, phosphate-buffered saline; PDGF-B, platelet-derived growth factor B; SFK, Src family kinase; SH, Src homology.…”

Section: Figurementioning

confidence: 99%

Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis

Yang

Dikici

et al. 2017

Annual Rev. Anal. Chem.

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The emergence of novel binding proteins or antibody mimetics capable of binding to ligand analytes in a manner analogous to that of the antigen–antibody interaction has spurred increased interest in the biotechnology and bioanalytical communities. The goal is to produce antibody mimetics designed to outperform antibodies with regard to binding affinities, cellular and tumor penetration, large-scale production, and temperature and pH stability. The generation of antibody mimetics with tailored characteristics involves the identification of a naturally occurring protein scaffold as a template that binds to a desired ligand. This scaffold is then engineered to create a superior binder by first creating a library that is then subjected to a series of selection steps. Antibody mimetics have been successfully used in the development of binding assays for the detection of analytes in biological samples, as well as in separation methods, cancer therapy, targeted drug delivery, and in vivo imaging. This review describes recent advances in the field of antibody mimetics and their applications in bioanalytical chemistry, specifically in diagnostics and other analytical methods.

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Isolation and Characterization of a Monobody with a Fibronectin Domain III Scaffold That Specifically Binds EphA2

Cited by 24 publications

References 44 publications

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

Engineering of monobody conjugates for human EphA2-specific optical imaging

Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis

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