dc.contributor.author
Bender, Martin
dc.contributor.author
Abicht, Jan-Michael
dc.contributor.author
Reichart, Bruno
dc.contributor.author
Neumann, Elisabeth
dc.contributor.author
Radan, Julia
dc.contributor.author
Mokelke, Maren
dc.contributor.author
Buttgereit, Ines
dc.contributor.author
Leuschen, Maria
dc.contributor.author
Wall, Felicia
dc.contributor.author
Michel, Sebastian
dc.contributor.author
Ellgass, Reinhard
dc.contributor.author
Steen, Stig
dc.contributor.author
Paskevicius, Audrius
dc.contributor.author
Lange, Andreas
dc.contributor.author
Kessler, Barbara
dc.contributor.author
Kemter, Elisabeth
dc.contributor.author
Klymiuk, Nikolai
dc.contributor.author
Denner, Joachim
dc.contributor.author
Godehardt, Antonia W.
dc.contributor.author
Tönjes, Ralf R.
dc.contributor.author
Burgmann, Jonathan M.
dc.contributor.author
Figueiredo, Constança
dc.contributor.author
Milusev, Anastasia
dc.contributor.author
Zollet, Valentina
dc.contributor.author
Salimi-Afjani, Neda
dc.contributor.author
Despont, Alain
dc.contributor.author
Rieben, Robert
dc.contributor.author
Ledderose, Stephan
dc.contributor.author
Walz, Christoph
dc.contributor.author
Hagl, Christian
dc.contributor.author
Ayares, David
dc.contributor.author
Wolf, Eckhard
dc.contributor.author
Schmoeckel, Michael
dc.contributor.author
Brenner, Paolo
dc.contributor.author
Binder, Uli
dc.contributor.author
Gebauer, Michaela
dc.contributor.author
Skerra, Arne
dc.contributor.author
Längin, Matthias
dc.date.accessioned
2024-08-29T11:02:54Z
dc.date.available
2024-08-29T11:02:54Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/44732
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-44443
dc.description.abstract
The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint.
en
dc.format.extent
21 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
co-stimulation blockade
en
dc.subject
orthotopic heart transplantation
en
dc.subject
xenotransplantation
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::617 Chirurgie und verwandte medizinische Einrichtungen
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
dc.title
Combination of Anti-CD40 and Anti-CD40L Antibodies as Co-Stimulation Blockade in Preclinical Cardiac Xenotransplantation
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1927
dcterms.bibliographicCitation.doi
10.3390/biomedicines12081927
dcterms.bibliographicCitation.journaltitle
Biomedicines
dcterms.bibliographicCitation.number
8
dcterms.bibliographicCitation.originalpublishername
MDPI
dcterms.bibliographicCitation.volume
12
dcterms.bibliographicCitation.url
https://doi.org/10.3390/biomedicines12081927
refubium.affiliation
Veterinärmedizin
refubium.affiliation.other
Institut für Virologie
![This authority value has been confirmed as accurate by an interactive user](/cache_202e45ad85b55efaeb29160f63cd3f3b/themes/FuCD/images/authority_control/invisible.gif)
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2227-9059