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

Publisher: Munksgaard International Publishers Country of Publication: Denmark NLM ID: 9438793 Publication Model: Print Cited Medium: Internet ISSN: 1399-3089 (Electronic) Linking ISSN: 0908665X NLM ISO Abbreviation: Xenotransplantation Subsets: MEDLINE

Publication: Copenhagen : Munksgaard International Publishers
Original Publication: Copenhagen : Munksgaard, c1994-

Macaca mulatta* ; Transplantation, Heterologous*/methods ; Graft Survival*/immunology ; Graft Survival*/drug effects ; Kidney Transplantation*/methods ; Immunosuppressive Agents*/pharmacology ; Heterografts*/immunology; Animals ; Swine ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacology ; Animals, Genetically Modified ; Antibodies, Monoclonal/pharmacology ; Humans ; Galactosyltransferases/genetics

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.
(© 2024 The Author(s). Xenotransplantation published by Wiley Periodicals LLC.)

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UO1 AI 126322 NIH NIAID; Novartis

Keywords: anti‐CD40 costimulation blockade; anti‐complement therapy; kidney transplantation; xenotransplantation

0 (Immunosuppressive Agents)
0 (Antibodies, Monoclonal, Humanized)
0 (Antibodies, Monoclonal)
EC 2.4.1.- (Galactosyltransferases)
EC 2.4.1.- (alpha-1,3-galactosyltransferase 1, porcine)

Date Created: 20240826 Date Completed: 20240826 Latest Revision: 20240826

20240826

10.1111/xen.12880

39185772