LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Erweiterte Suche

Suchergebnis

Treffer 1 - 2 von insgesamt 2

Suchoptionen

  1. Artikel ; Online: High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models.

    Degagné, Émilie / Donohoue, Paul D / Roy, Suparna / Scherer, Jessica / Fowler, Tristan W / Davis, Ryan T / Reyes, Gustavo A / Kwong, George / Stanaway, Morena / Larroca Vicena, Vanina / Mutha, Devin / Guo, Raymond / Edwards, Leslie / Schilling, Benjamin / Shaw, McKay / Smith, Stephen C / Kohrs, Bryan / Kufeldt, Heinrich J / Churchward, Glen /
    Ruan, Finey / Nyer, David B / McSweeney, Kyle / Irby, Matthew J / Fuller, Christopher K / Banh, Lynda / Toh, Mckenzi S / Thompson, Matthew / Owen, Arthur L G / An, Zili / Gradia, Scott / Skoble, Justin / Bryan, Mara / Garner, Elizabeth / Kanner, Steven B

    Cancer immunology research

    2024  Band 12, Heft 4, Seite(n) 462–477

    Abstract: Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include ... ...

    Abstract Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti-B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were engineered from healthy donor-derived T cells using a Cas12a CRISPR hybrid RNA-DNA (chRDNA) genome-editing technology platform. To address allograft rejection, CAR T cells were engineered to prevent endogenous HLA class I complex expression and overexpress a single-chain polyprotein complex composed of beta-2 microglobulin (B2M) tethered to HLA-E. In addition, T-cell receptor (TCR) expression was disrupted at the TCR alpha constant locus in combination with the site-specific insertion of a humanized BCMA-specific CAR. CB-011 cells exhibited robust plasmablast cytotoxicity in vitro in a mixed lymphocyte reaction in cell cocultures derived from patients with multiple myeloma. In addition, CB-011 cells demonstrated suppressed recognition by and cytotoxicity from HLA-mismatched T cells. CB-011 cells were protected from natural killer cell-mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M-HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma. See related Spotlight by Caimi and Melenhorst, p. 385.
    Mesh-Begriff(e) Humans ; Multiple Myeloma/genetics ; Multiple Myeloma/therapy ; B-Cell Maturation Antigen/metabolism ; HLA-E Antigens ; T-Lymphocytes ; Receptors, Antigen, T-Cell ; Immunotherapy, Adoptive ; Histocompatibility Antigens Class I/metabolism ; Hematopoietic Stem Cell Transplantation ; Allografts/pathology
    Chemische Substanzen B-Cell Maturation Antigen ; HLA-E Antigens ; Receptors, Antigen, T-Cell ; Histocompatibility Antigens Class I
    Sprache Englisch
    Erscheinungsdatum 2024-02-12
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-23-0679
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 7022: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  2. Artikel ; Online: Alternative complexes formed by the Escherichia coli clamp loader accessory protein HolC (x) with replication protein HolD (ψ) and repair protein YoaA.

    Sutera, Vincent A / Weeks, Savannah J / Dudenhausen, Elizabeth E / Baggett, Helen B Rappe / Shaw, McKay C / Brand, Kirsten A / Glass, David J / Bloom, Linda B / Lovett, Susan T

    DNA repair

    2021  Band 100, Seite(n) 103006

    Abstract: Efficient and faithful replication of DNA is essential for all organisms. However, the replication fork frequently encounters barriers that need to be overcome to ensure cell survival and genetic stability. Cells must carefully balance and regulate ... ...

    Abstract Efficient and faithful replication of DNA is essential for all organisms. However, the replication fork frequently encounters barriers that need to be overcome to ensure cell survival and genetic stability. Cells must carefully balance and regulate replication vs. repair reactions. In Escherichia coli, the replisome consists of the DNA polymerase III holoenzyme, including DNA polymerase, proofreading exonuclease, processivity clamp and clamp loader, as well as a fork helicase, DnaB and primase, DnaG. We provide evidence here that one component of the clamp loader complex, HolC (or χ) plays a dual role via its ability to form 2 mutually exclusive complexes: one with HolD (or ψ) that recruits the clamp-loader and hence the DNA polymerase holoenzyme and another with helicase-like YoaA protein, a DNA-damage inducible repair protein. By yeast 2 hybrid analysis, we show that two residues of HolC, F64 and W57, at the interface in the structure with HolD, are required for interaction with HolD and for interaction with YoaA. Mutation of these residues does not interfere with HolC's interaction with single-strand DNA binding protein, SSB. In vivo, these mutations fail to complement the poor growth and sensitivity to azidothymidine, a chain-terminating replication inhibitor. In support of the notion that these are exclusive complexes, co-expression of HolC, HolD and YoaA, followed by pulldown of YoaA, yields a complex with HolC but not HolD. YoaA fails to pulldown HolC-F64A. We hypothesize that HolC, by binding with SSB, can recruit the DNA polymerase III holoenzyme through HolD, or an alternative repair complex with YoaA helicase.
    Mesh-Begriff(e) DNA Polymerase III/metabolism ; DNA Repair ; DNA Replication ; DNA, Bacterial/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/metabolism ; Protein Binding ; Protein Conformation
    Chemische Substanzen DNA, Bacterial ; Escherichia coli Proteins ; holD protein, E coli ; DNA Polymerase III (EC 2.7.7.7) ; holC protein, E coli (EC 2.7.7.7)
    Sprache Englisch
    Erscheinungsdatum 2021-02-02
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 2071608-4
    ISSN 1568-7856 ; 1568-7864
    ISSN (online) 1568-7856
    ISSN 1568-7864
    DOI 10.1016/j.dnarep.2020.103006
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 5555: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

Zum Seitenanfang