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. 2024 Jul-Aug;31(4):e12880.
doi: 10.1111/xen.12880.

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

Andrew B Adams  1 , David Faber  1 , Brendan P Lovasik  2 , Abraham J Matar  1 , Steven C Kim  2 , Christopher Burlak  3 , Matt Tector  4 , Alfred J Tector  3
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Iscalimab Combined With Transient Tesidolumab Prolongs Survival in Pig-to-Rhesus Monkey Renal Xenografts

Andrew B Adams et al. Xenotransplantation. 2024 Jul-Aug.

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.

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

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References

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    1. S. C. Kim, D. V. Mathews, C. P. Breeden, et al., “Long‐Term Survival of Pig‐to‐Rhesus Macaque Renal Xenografts Is Dependent on CD4 T Cell Depletion,” American Journal of Transplantation 19, no. 8 (2019): 2174–2185.
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    1. Y. Cui, T. Yamamoto, S. S. Raza, et al., “Evidence for GTKO/beta4GalNT2KO Pigs as the Preferred Organ‐Source for Old World Nonhuman Primates as a Preclinical Model of Xenotransplantation,” Transplant Direct 6, no. 8 (2020): e590.

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