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Titel: Cytomegalovirus-Specific T-Cell-Receptor-like Antibodies Target In Vivo-Infected Human Leukocytes Inducing Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity
VerfasserIn: Bewarder, Moritz
Christofyllakis, Konstantinos
Petersen, Milena
Held, Gerhard
Smola, Sigrun
Carbon, Gabi
Bette, Birgit
Link, Annika
Kiefer, Maximilian
Bittenbring, Joerg Thomas
Kos, Igor Age
Lesan, Vadim
Kaddu-Mulindwa, Dominic
Thurner, Lorenz
Neumann, Frank
Sprache: Englisch
Titel: International Journal of Molecular Sciences
Bandnummer: 25
Heft: 23
Verlag/Plattform: MDPI
Erscheinungsjahr: 2024
Freie Schlagwörter: cytomegalovirus
T-cell receptor (TCR)-like antibodies
human leukocyte antigen (HLA) alleles
stem cell transplantation
solid organ transplantation
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Cytomegalovirus (CMV) reactivation after stem cell or solid organ transplantation remains a major cause of morbidity and mortality in this setting. T-cell receptor (TCR)-like antibodies bind to intracellular peptides presented in major histocompatibility complex (MHC) molecules on the cell surface and may have the potential to replace T-cell function in immunocompromised patients. Three previously selected CMV-specific, human leukocyte antigen (HLA)-restricted (HLA-A*0101, HLA-A*0201 and HLA-B*0702) Fab-antibodies (A6, C1 and C7) were produced as IgG antibodies with Fc optimization. All antibodies showed specific binding to CMV peptide-loaded tumor cell lines and primary fibroblasts expressing the corresponding MHC-I molecules, leading to specific target cell lysis after the addition of natural killer (NK) cells. When deployed in combination as an antibody pool against target cells expressing more than one matching HLA allele, cytotoxic effects were amplified accordingly. CMV-specific TCR-like antibodies were also able to mediate their cytotoxic effects through neutrophils, which is important considering the delayed recovery of NK cells after stem cell transplantation. When tested on patient blood obtained during CMV reactivation, CMV-specific antibodies were able to bind to and induce cytotoxic effects in lymphocytes. CMV-specific TCR-like antibodies may find application in patients with CMV reactivation or at risk of CMV reactivation. In contrast to previous HLA/peptide-directed therapeutic approaches, the concept of a TCR-like antibody repertoire covering more than one HLA allele would make this therapeutic format available to a much larger group of patients.
DOI der Erstveröffentlichung: 10.3390/ijms252312908
URL der Erstveröffentlichung: https://doi.org/10.3390/ijms252312908
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-437746
hdl:20.500.11880/39194
http://dx.doi.org/10.22028/D291-43774
ISSN: 1422-0067
Datum des Eintrags: 16-Dez-2024
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Materials
In Beziehung stehendes Objekt: https://www.mdpi.com/article/10.3390/ijms252312908/s1
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Infektionsmedizin
M - Innere Medizin
Professur: M - Prof. Dr. Sigrun Smola
M - Prof. Dr. Stephan Stilgenbauer
M - Dr. med. Lorenz Thurner
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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