Iscalimab Combined With Transient Tesidolumab Prolongs Survival in Pig‐to‐Rhesus Monkey Renal Xenografts

ABSTRACT Objective To evaluate the clinically relevant anti‐CD40 antibody iscalimab for baseline immunosuppression in a preclinical pig‐to‐rhesus renal xenograft model. Summary Background Data CD40/CD40L co‐stimulation blockade‐based immunosuppression has been more successful than calcineurin‐based...

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Published in:Xenotransplantation (Københaven) 2024-07, Vol.31 (4), p.e12880-n/a
Main Authors: Adams, Andrew B., Faber, David, Lovasik, Brendan P., Matar, Abraham J., Kim, Steven C., Burlak, Christopher, Tector, Matt, Tector, Alfred J.
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
anti‐CD40 costimulation blockade
anti‐complement therapy
Galactosyltransferases - genetics
Graft Rejection - immunology
Graft Rejection - prevention & control
Graft Survival - drug effects
Graft Survival - immunology
Heterografts - immunology
Humans
Immunosuppressive Agents - pharmacology
kidney transplantation
Kidney Transplantation - methods
Macaca mulatta
Swine
Transplantation, Heterologous - methods
xenotransplantation
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Summary:ABSTRACT Objective To evaluate the clinically relevant anti‐CD40 antibody iscalimab for baseline immunosuppression in a preclinical pig‐to‐rhesus renal xenograft model. Summary Background Data CD40/CD40L co‐stimulation blockade‐based immunosuppression has been more successful than calcineurin‐based protocols in prolonging xenograft survival in preclinical models. Methods GGTA1 knockout/CD55 transgenic pig kidneys were transplanted into rhesus monkeys (n = 6) receiving an iscalimab‐based immunosuppressive regimen. Results Two grafts were lost early (22 and 26 days) because of ectatic donor ureters with otherwise normal histology. The other recipients survived 171, 315, 422, and 439 days with good renal function throughout the posttransplant course. None of the recipients experienced serious infectious morbidity. Conclusions It may be reasonable to evaluate an iscalimab‐based immunosuppressive regimen in clinical renal xenotransplantation.
ISSN:0908-665X
1399-3089
1399-3089
DOI:10.1111/xen.12880