Kidney Week

Abstract: SA-OR47

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

Session Information

• Transplantation: Clinical Outcomes and Biomarkers
  November 05, 2022 | Location: W240, Orange County Convention Center‚ West Building
  Abstract Time: 05:24 PM - 05:33 PM

Category: Transplantation

• 2002 Transplantation: Clinical

Authors

• Schaier, Matthias, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Matthias Schaier, MD, MBA

• Morath, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Christian Morath,

• Wang, Lei, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Lei Wang,

• Kleist, Christian, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Christian Kleist,

• Opelz, Gerhard, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Gerhard Opelz,

• Tran, Thuong Hien, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Thuong Hien Tran,

• Scherer, Sabine, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Sabine Scherer,

• Süsal, Caner, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Caner Süsal,

• Ibrahim, Eman Hosny, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Eman Hosny Ibrahim,

• Aly, Mostafa Gaafar, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Mostafa Gaafar Aly,

• Alvarez, Cristian M., Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Cristian M. Alvarez,

• Hückelhoven-Krauss, Angela, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Angela Hückelhoven-Krauss,

• Czock, David, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

David Czock,

• Mehrabi, Arianeb, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Arianeb Mehrabi,

• Schwab, Constantin, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Constantin Schwab,

• Waldherr, Ruediger, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Ruediger Waldherr,

• Schnitzler, Paul, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Paul Schnitzler,

• Merle, Uta, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Uta Merle,

• Bohmig, Georg, Medizinische Universitat Wien Universitatsklinik fur Innere Medizin III, Wien, Wien, Austria

Georg Bohmig,

• Reiser, Jochen, Rush University Rush Medical College, Chicago, Illinois, United States

Jochen Reiser,

• Zeier, Martin G., Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Martin G. Zeier,

• Schmitt, Michael, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Michael Schmitt,

• Terness, Peter, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Peter Terness,

• Schmitt, Anita, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Anita Schmitt,

• Daniel, Volker, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Volker Daniel,

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⁺CD24^hiCD38^hi transitional Breg as well as CD19⁺CD24^hiCD27⁺ 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 –