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Abstract: SA-OR47

Five-Year Follow-Up of a Phase 1 Trial of Donor-Derived Modified Immune Cell Infusion in Kidney Transplantation

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Schaier, Matthias, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Morath, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Wang, Lei, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Kleist, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Opelz, Gerhard, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Tran, Thuong Hien, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Scherer, Sabine, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Süsal, Caner, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Ibrahim, Eman Hosny, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Aly, Mostafa Gaafar, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Alvarez, Cristian M., Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Hückelhoven-Krauss, Angela, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Czock, David, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Mehrabi, Arianeb, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Schwab, Constantin, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Waldherr, Ruediger, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Schnitzler, Paul, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Merle, Uta, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Bohmig, Georg, Medizinische Universitat Wien Universitatsklinik fur Innere Medizin III, Wien, Wien, Austria
  • Reiser, Jochen, Rush University Rush Medical College, Chicago, Illinois, United States
  • Zeier, Martin G., Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Schmitt, Michael, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Terness, Peter, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Schmitt, Anita, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Daniel, Volker, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Group or Team Name

  • TOL-1 Study group at Nierenzentrum Heidelberg
Background

The administration of modified immune cells (MIC) prior to kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes (Breg) (Morath et al., J Clin Invest 2020). We now wanted to investigate how this approach affects the clinical course of treated patients.

Methods

Clinical results of ten patients from a phase I clinical trial who had received MIC infusions before kidney transplantation were compared to results of 15 matched standard-risk recipients. Follow-up was until year five after surgery.

Results

The 10 MIC patients had an excellent clinical course with stable kidney graft function and showed no donor-specific human leukocyte antigen antibodies (DSA) or acute rejections during follow-up. In contrast, 1 of 15 controls died and 5 of 15 controls developed DSA (log rank P = 0.046) (Figure 1 A, B). While the number of patients with a non-opportunistic infection did not differ significantly between groups (P = 0.36), opportunistic infections were reported more frequently in controls (log rank P = 0.033) (Figure 1 C). Compared to controls, MIC patients were found to have a trend towards a higher COVID-19 anti-S1 IgG index after vaccination with a median of 53 vs. 2 (P = 0.16). Importantly, the four MIC patients who had received the highest MIC cell dose 7 days before surgery and were on low immunosuppression during follow-up, continued to show absent anti-donor T lymphocyte reactivity in vitro and high CD19+CD24hiCD38hi transitional Breg as well as CD19+CD24hiCD27+ memory Breg.

Conclusion

MIC infusions together with reduced conventional immunosuppression were associated with lower de novo DSA development and lower rates of opportunistic infections. In the future, MIC infusions could contribute to graft protection while reducing the side effects of immunosuppressive therapy.

Funding

  • Commercial Support