Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Schreiber, Sophia [VerfasserIn]   i
 Dressler, Lisa S. [VerfasserIn]   i
 Loffredo-Verde, Eva [VerfasserIn]   i
 Asen, Theresa [VerfasserIn]   i
 Färber, Stephanie [VerfasserIn]   i
 Wang, Wenshi [VerfasserIn]   i
 Groll, Tanja [VerfasserIn]   i
 Chakraborty, Anindita [VerfasserIn]   i
 Kolbe, Fenna [VerfasserIn]   i
 Kreer, Christoph [VerfasserIn]   i
 Kosinska, Anna D. [VerfasserIn]   i
 Simon, Sylvain [VerfasserIn]   i
 Urban, Stephan [VerfasserIn]   i
 Klein, Florian [VerfasserIn]   i
 Riddell, Stanley R. [VerfasserIn]   i
 Protzer, Ulrike [VerfasserIn]   i
Titel:CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells
Verf.angabe:Sophia Schreiber, Lisa S. Dressler, Eva Loffredo-Verde, Theresa Asen, Stephanie Färber, Wenshi Wang, Tanja Groll, Anindita Chakraborty, Fenna Kolbe, Christoph Kreer, Anna D. Kosinska, Sylvain Simon, Stephan Urban, Florian Klein, Stanley R. Riddell and Ulrike Protzer
E-Jahr:2024
Jahr:22 April 2024
Umfang:14 S.
Fussnoten:Gesehen am 24.03.2025
Titel Quelle:Enthalten in: Frontiers in immunology
Ort Quelle:Lausanne : Frontiers Media, 2010
Jahr Quelle:2024
Band/Heft Quelle:15(2024), Artikel-ID 1340619, Seite 1-14
ISSN Quelle:1664-3224
Abstract:To design new CARs targeting hepatitis B virus (HBV), we isolated human monoclonal antibodies recognizing the HBV envelope proteins from single B cells of a patient with a resolved infection. HBV-specific memory B cells were isolated by incubating peripheral blood mononuclear cells with biotinylated hepatitis B surface antigen (HBsAg), followed by single-cell flow cytometry-based sorting of live, CD19+ IgG+ HBsAg+ cells. Amplification and sequencing of immunoglobulin genes from single memory B cells identified variable heavy and light chain sequences. Corresponding immunoglobulin chains were cloned into IgG1 expression vectors and expressed in mammalian cells. Two antibodies named 4D06 and 4D08 were found to be highly specific for HBsAg, recognized a conformational and a linear epitope, respectively, and showed broad reactivity and neutralization capacity against all major HBV genotypes. 4D06 and 4D08 variable chain fragments were cloned into a 2nd generation CAR format with CD28 and CD3zeta intracellular signaling domains. The new CAR constructs displayed a high functional avidity when expressed on primary human T cells. CAR-grafted T cells proved to be polyfunctional regarding cytokine secretion and killed HBV-positive target cells. Interestingly, background activation of the 4D08-CAR recognizing a linear instead of a conformational epitope was consistently low. In a preclinical model of chronic HBV infection, murine T cells grafted with the 4D06 and the 4D08 CAR showed on target activity indicated by a transient increase in serum transaminases, and a lower number of HBV-positive hepatocytes in the mice treated. This study demonstrates an efficient and fast approach to identifying pathogen-specific monoclonal human antibodies from small donor cell numbers for the subsequent generation of new CARs.
DOI:doi:10.3389/fimmu.2024.1340619
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.3389/fimmu.2024.1340619
 DOI: https://doi.org/10.3389/fimmu.2024.1340619
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Animals
 Antibodies, Monoclonal
 B-Lymphocytes
 broad neutralization
 Broadly Neutralizing Antibodies
 chimeric antigen receptor
 HBsAg
 Hepatitis B
 Hepatitis B Surface Antigens
 Hepatitis B virus
 hepatitis B virus envelope proteins
 human monoclonal antibody
 Humans
 Immunotherapy, Adoptive
 linear epitope
 Mice
 Receptors, Chimeric Antigen
 single B cell sorting
 T-Lymphocytes
 tonic signaling
K10plus-PPN:1920399933
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/69321428   QR-Code
zum Seitenanfang