Martin Bender, Jan-Michael Abicht, Bruno Reichart, Elisabeth Neumann, Julia Radan, Maren Mokelke, Ines Buttgereit, Maria Leuschen, Felicia Wall, Sebastian Michel, Reinhard Ellgass, Stig Steen, Audrius Paskevicius, Andreas Lange, Barbara Kessler, Elisabeth Kemter, Nikolai Klymiuk, Joachim Denner, Antonia W Godehardt, Ralf R Tönjes, Jonathan M Burgmann, Constança Figueiredo, Anastasia Milusev, Valentina Zollet, Neda Salimi-Afjani, Alain Despont, Robert Rieben, Stephan Ledderose, Christoph Walz, Christian Hagl, David Ayares, Eckhard Wolf, Michael Schmoeckel, Paolo Brenner, Uli Binder, Michaela Gebauer, Arne Skerra, Matthias Längin
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...
August 22, 2024: Biomedicines