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  1. Article ; Online: Clinical Validation of a Novel T-cell Receptor Sequencing Assay for Identification of Recent or Prior SARS-CoV-2 Infection.

    Dalai, Sudeb C / Dines, Jennifer N / Snyder, Thomas M / Gittelman, Rachel M / Eerkes, Tera / Vaney, Pashmi / Howard, Sally / Akers, Kipp / Skewis, Lynell / Monteforte, Anthony / Witte, Pamela R / Wolf, Cristina / Nesse, Hans / Herndon, Megan / Qadeer, Jia / Duffy, Sarah / Svejnoha, Emily / Taromino, Caroline / Kaplan, Ian M /
    Alsobrook, John / Manley, Thomas / Baldo, Lance

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2022  

    Abstract: Background: While diagnostic, therapeutic, and vaccine development in the COVID-19 pandemic has proceeded at unprecedented speed, critical gaps in our understanding of the immune response to SARS-CoV-2 remain unaddressed by current diagnostic strategies. ...

    Abstract Background: While diagnostic, therapeutic, and vaccine development in the COVID-19 pandemic has proceeded at unprecedented speed, critical gaps in our understanding of the immune response to SARS-CoV-2 remain unaddressed by current diagnostic strategies.
    Methods: A statistical classifier for identifying prior SARS-CoV-2 infection was trained using >4000 SARS-CoV-2-associated TCRβ sequences identified by comparing 784 cases and 2447 controls from 5 independent cohorts. The T-Detect™ COVID assay applies this classifier to TCR repertoires sequenced from blood samples to yield a binary assessment of past infection. Assay performance was assessed in 2 retrospective (n = 346; n = 69) and 1 prospective cohort (n = 87) to determine positive percent agreement (PPA) and negative percent agreement (NPA). PPA was compared to 2 commercial serology assays, and pathogen cross-reactivity was evaluated.
    Results: T-Detect COVID demonstrated high PPA in individuals with prior RT-PCR-confirmed SARS-CoV-2 infection (97.1% 15 + days from diagnosis; 94.5% 15 + days from symptom onset), high NPA (∼100%) in presumed or confirmed SARS-CoV-2 negative cases, equivalent or higher PPA than 2 commercial serology tests, and no evidence of pathogen cross-reactivity.
    Conclusion: T-Detect COVID is a novel T-cell immunosequencing assay demonstrating high clinical performance for identification of recent or prior SARS-CoV-2 infection from blood samples, with implications for clinical management, risk stratification, surveillance, and understanding protective immunity and long-term sequelae.
    Language English
    Publishing date 2022-05-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciac353
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1505: Show issues Location:
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  2. Article ; Online: *

    Monteforte, Anthony / Lam, Brian / Sherman, Michael B / Henderson, Kayla / Sligar, Andrew D / Spencer, Adrianne / Tang, Brian / Dunn, Andrew K / Baker, Aaron B

    Tissue engineering. Part A

    2017  Volume 23, Issue 21-22, Page(s) 1251–1261

    Abstract: Peripheral ischemia as a result of occlusive vascular disease is a widespread problem in patients older than the age of 65. Angiogenic therapies that can induce microvascular growth have great potential for providing a long-lasting solution for patients ... ...

    Abstract Peripheral ischemia as a result of occlusive vascular disease is a widespread problem in patients older than the age of 65. Angiogenic therapies that can induce microvascular growth have great potential for providing a long-lasting solution for patients with ischemia and would provide an appealing alternative to surgical and percutaneous interventions. However, many angiogenic therapies have seen poor efficacy in clinical trials, suggesting that patients with long-term peripheral ischemia have considerable therapeutic resistance to angiogenic stimuli. Glioblastoma is one of the most angiogenic tumor types, inducing robust vessel growth in the area surrounding the tumor. One major angiogenic mechanism used by the tumor cells to induce blood vessel growth is the production of exosomes and other extracellular vesicles that can carry pro-angiogenic and immunomodulatory signals. Here, we explored whether the pro-angiogenic aspects of glioblastoma-derived exosomes could be harnessed to promote angiogenesis and healing in the context of peripheral ischemic disease. We demonstrate that the exosomes derived from glioblastoma markedly enhance endothelial cell proliferation and increase endothelial tubule formation in vitro. An analysis of the microRNA expression using next generation sequencing identified that exosomes contained a high concentration of miR-221. In addition, we found that glioblastoma exosomes contained significant amounts of the proteoglycans glypican-1 and syndecan-4, which can serve as co-receptors for angiogenic factors, including fibroblast growth factor-2 (FGF-2). In a hindlimb ischemia model in mice, we found that the exosomes promoted enhanced revascularization in comparison to control alginate gels and FGF-2 treatment alone. Taken together, our results support the fact that glioblastoma-derived exosomes have powerful effects in increasing revascularization in the context of peripheral ischemia.
    MeSH term(s) Animals ; Brain Neoplasms/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Exosomes/metabolism ; Exosomes/ultrastructure ; Fibroblast Growth Factor 2/pharmacology ; Fibroblast Growth Factor 2/therapeutic use ; Glioblastoma/metabolism ; Hindlimb/blood supply ; Hindlimb/pathology ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Ischemia/drug therapy ; Ischemia/therapy ; Mice, Inbred C57BL ; Neovascularization, Physiologic/drug effects ; RNA, Neoplasm/metabolism
    Chemical Substances RNA, Neoplasm ; Fibroblast Growth Factor 2 (103107-01-3)
    Language English
    Publishing date 2017-07-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2420582-5
    ISSN 1937-335X ; 1937-3341
    ISSN (online) 1937-335X
    ISSN 1937-3341
    DOI 10.1089/ten.TEA.2016.0508
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  3. Article ; Online: Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes.

    Das, Subhamoy / Monteforte, Anthony J / Singh, Gunjan / Majid, Marjan / Sherman, Michael B / Dunn, Andrew K / Baker, Aaron B

    Advanced healthcare materials

    2016  Volume 5, Issue 9, Page(s) 1008–1013

    Abstract: Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ... ...

    Abstract Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ischemic hind limbs of diseased ob/ob mice. Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype.
    Language English
    Publishing date 2016-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.201500993
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  4. Article ; Online: Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis.

    Monteforte, Anthony J / Lam, Brian / Das, Subhamoy / Mukhopadhyay, Somshuvra / Wright, Catherine S / Martin, Patricia E / Dunn, Andrew K / Baker, Aaron B

    Biomaterials

    2016  Volume 94, Page(s) 45–56

    Abstract: Therapeutic angiogenesis is a highly appealing concept for treating tissues that become ischemic due to vascular disease. A major barrier to the clinical translation of angiogenic therapies is that the patients that are in the greatest need of these ... ...

    Abstract Therapeutic angiogenesis is a highly appealing concept for treating tissues that become ischemic due to vascular disease. A major barrier to the clinical translation of angiogenic therapies is that the patients that are in the greatest need of these treatments often have long term disease states and co-morbidities, such as diabetes and obesity, that make them resistant to angiogenic stimuli. In this study, we identified that human patients with type 2 diabetes have reduced levels of glypican-1 in the blood vessels of their skin. The lack of this key co-receptor in the tissue may make the application of exogenous angiogenic growth factors or cell therapies ineffective. We created a novel therapeutic enhancer for growth factor activity consisting of glypican-1 delivered in a nanoliposomal carrier (a "glypisome"). Here, we demonstrate that glypisomes enhance FGF-2 mediated endothelial cell proliferation, migration and tube formation. In addition, glypisomes enhance FGF-2 trafficking by increasing both uptake and endosomal processing. We encapsulated FGF-2 or FGF-2 with glypisomes in alginate beads and used these to deliver localized growth factor therapy in a murine hind limb ischemia model. Co-delivery of glypisomes with FGF-2 markedly increased the recovery of perfusion and vessel formation in ischemic hind limbs of wild type and diabetic mice in comparison to mice treated with FGF-2 alone. Together, our findings support that glypisomes are effective means for enhancing growth factor activity and may improve the response to local angiogenic growth factor therapies for ischemia.
    Language English
    Publishing date 2016-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2016.03.048
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    Zs.B 2371: Show issues Location:
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  5. Article: Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis

    Monteforte, Anthony J / Lam, Brian / Das, Subhamoy / Mukhopadhyay, Somshuvra / Wright, Catherine S / Martin, Patricia E / Dunn, Andrew K / Baker, Aaron B

    Biomaterials. 2016 July, v. 94

    2016  

    Abstract: Therapeutic angiogenesis is a highly appealing concept for treating tissues that become ischemic due to vascular disease. A major barrier to the clinical translation of angiogenic therapies is that the patients that are in the greatest need of these ... ...

    Abstract Therapeutic angiogenesis is a highly appealing concept for treating tissues that become ischemic due to vascular disease. A major barrier to the clinical translation of angiogenic therapies is that the patients that are in the greatest need of these treatments often have long term disease states and co-morbidities, such as diabetes and obesity, that make them resistant to angiogenic stimuli. In this study, we identified that human patients with type 2 diabetes have reduced levels of glypican-1 in the blood vessels of their skin. The lack of this key co-receptor in the tissue may make the application of exogenous angiogenic growth factors or cell therapies ineffective. We created a novel therapeutic enhancer for growth factor activity consisting of glypican-1 delivered in a nanoliposomal carrier (a “glypisome”). Here, we demonstrate that glypisomes enhance FGF-2 mediated endothelial cell proliferation, migration and tube formation. In addition, glypisomes enhance FGF-2 trafficking by increasing both uptake and endosomal processing. We encapsulated FGF-2 or FGF-2 with glypisomes in alginate beads and used these to deliver localized growth factor therapy in a murine hind limb ischemia model. Co-delivery of glypisomes with FGF-2 markedly increased the recovery of perfusion and vessel formation in ischemic hind limbs of wild type and diabetic mice in comparison to mice treated with FGF-2 alone. Together, our findings support that glypisomes are effective means for enhancing growth factor activity and may improve the response to local angiogenic growth factor therapies for ischemia.
    Keywords alginates ; angiogenesis ; animal disease models ; blood vessels ; cell proliferation ; endothelial cells ; growth factors ; hindlimbs ; ischemia ; mice ; noninsulin-dependent diabetes mellitus ; obesity ; patients ; therapeutics ; tissues
    Language English
    Dates of publication 2016-07
    Size p. 45-56.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2016.03.048
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Clinical Validation of a Novel T-cell Receptor Sequencing Assay for Identification of Recent or Prior SARS-CoV-2 Infection

    Dalai, Sudeb C. / Dines, Jennifer N. / Snyder, Thomas M. / Gittelman, Rachel M. / Eerkes, Tera / Vaney, Pashmi / Howard, Sally / Akers, Kipp / Skewis, Lynell / Monteforte, Anthony / Witte, Pam / Wolf, Cristina / Nesse, Hans / Herndon, Megan / Qadeer, Jia / Duffy, Sarah / Svejnoha, Emily / Taromino, Caroline / Kaplan, Ian M. /
    Alsobrook, John / Manley, Thomas / Baldo, Lance

    medRxiv

    Abstract: Background While diagnostic, therapeutic, and vaccine development in the COVID-19 pandemic has proceeded at unprecedented speed and scale, critical gaps remain in our understanding of the immune response to SARS-CoV-2. Current diagnostic strategies, ... ...

    Abstract Background While diagnostic, therapeutic, and vaccine development in the COVID-19 pandemic has proceeded at unprecedented speed and scale, critical gaps remain in our understanding of the immune response to SARS-CoV-2. Current diagnostic strategies, including serology, have numerous limitations in addressing these gaps. Here we describe clinical performance of T-Detect™ COVID, the first reported assay to determine recent or prior SARS-CoV-2 infection based on T-cell receptor (TCR) sequencing and immune repertoire profiling from whole blood samples. Methods Methods for high-throughput immunosequencing of the TCRβ gene from blood specimens have been described<sup>1</sup>. We developed a statistical classifier showing high specificity for identifying prior SARS-CoV-2 infection<sup>2</sup>, utilizing >4,000 SARS-CoV-2-associated TCR sequences from 784 cases and 2,447 controls across 5 independent cohorts. The T-Detect COVID Assay comprises immunosequencing and classifier application to yield a qualitative positive or negative result. Several retrospective and prospective cohorts were enrolled to assess assay performance including primary and secondary Positive Percent Agreement (PPA; N=205, N=77); primary and secondary Negative Percent Agreement (NPA; N=87, N=79); PPA compared to serology (N=55); and pathogen cross-reactivity (N=38). Results T-Detect COVID demonstrated high PPA in subjects with prior PCR-confirmed SARS-CoV-2 infection (97.1% 15+ days from diagnosis; 94.5% 15+ days from symptom onset), high NPA (~100%) in presumed or confirmed SARS-CoV-2 negative cases, equivalent or higher PPA than two commercial EUA serology tests, and no evidence of pathogen cross-reactivity. Conclusion T-Detect COVID is a novel T-cell immunosequencing assay demonstrating high clinical performance to identify recent or prior SARS-CoV-2 infection from standard blood samples. This assay can provide critical insights on the SARS-CoV-2 immune response, with potential implications for clinical management, risk stratification, surveillance, assessing protective immunity, and understanding long-term sequelae.
    Keywords covid19
    Language English
    Publishing date 2021-01-08
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.01.06.21249345
    Database COVID19

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