Back to 2026 Abstracts

---

Swine Leukocyte Antigen DR Deletion Is a Viable Option for Donor Pigs Used in Renal Xenotransplantation
Andrew B. Adams², *Matt Tector³, *Jose Estrada¹, *Luz Reyes¹, *sabrina cospel³, *Claudia Muniz³, *Victor Novara Gennuso¹, *Neal Iwakoshi², *Michael Dryden², *David Faber², *Bryan Ray⁴, *Holly Haver⁴, *Jayasree Hariharan⁴, *Rodrigo Vianna¹, *Alfred J. Tector^1
1surgery, university of miami, Miami, Florida; ²Surgery, University of Minnesota School of Medicine, Minneapolis, Minnesota; ³Makana Therapeutics, Miami, Florida; ⁴Werfen, Brookfield, Wisconsin

OBJECTIVES: Class II MHC is an important target for rejection in transplantation. Swine Luukocyte Antigen (SLA) DR is the dominant class II antigen in pig organs that are used for xenotransplantation. It is unclear whether it is feasible/safe to delete SLA DR in donor pigs to be used in kidney xenotransplantation. This study created prototype SLA DR knockout (KO) pigs and evaluated the safety infectious/profile and ability to function in a preclinical model of xenotransplantation.
METHODS: SLA DR KO pigs were created on an a-gal, Sd_a (GGTA1/B4GALNT2) deficient genetic background using CRISPR/Cas and somatic cell nuclear transfer. Pigs were evaluated for 55 potential zoonotic viral pathogens using digital droplet (dd) PCR assays developed in our lab. 4 GGTA1/B4GALNT2/SLA DR KO pig kidneys were transplanted to rhesus monkeys who received depletional induction immunosuppression and anti-CD154 maintenance immunosuppression. Graft survival and renal function were monitored to evaluate the ability of these prototype kidneys to provide life supporting renal function in a preclinical model.
RESULTS: SLA DR KO pigs were produced and are healthy and viable now more than 2 years old. SLA DR KO pigs were devoid of 55 viral pathogens determined to have zoonotic infectious potential. The 4 recipients survived 7, 126, and >338, >338 days. Serum creatinine was maintained in the long survivors Cr (0.8 mg/dL in both). The early graft losses (7 and 126 days) occurred because of donor specific pre-transplant SLA sensitization detected using our new SLA bead crossmatch assay.
CONCLUSIONS: SLA DR KO pigs are viable and are safe to consider as potential human donors from an infectious risk standpoint in clinical trials. The SLA DR KO pig kidneys provided good long term graft function in a preclinical model if the donor was not pre-sensitized to other SLA antigens present in the donor pig. The SLA DR KO prototype is promising for evaluation in pig-to-human clinical xenograft trials.