Kidney Week

Abstract: SA-PO996

Treating Refractory BK Virus Nephropathy with Allogenic BK Virus-Specific T Cells in Kidney Transplant Recipients

Session Information

• Transplantation: Clinical - 4
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2102 Transplantation: Clinical

Authors

• Chandwani, Suraj Jitendra, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Suraj Jitendra Chandwani

• Lonnemann, Eike, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Eike Lonnemann

• Tian, Zhejia, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Zhejia Tian

• Richter, Alena, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Alena Richter, MD

• Tischer-Zimmermann, Sabine, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Sabine Tischer-Zimmermann

• Bonifacius, Agnes, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Agnes Bonifacius

• Wintering, Astrid, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Astrid Wintering, MD

• Blasczyk, Rainer, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Rainer Blasczyk, MD

• Schmidt-Ott, Kai M., Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Kai M. Schmidt-Ott, MD, DrMed

• Gwinner, Wilfried, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Wilfried Gwinner, MD

• Eiz-Vesper, Britta, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Britta Eiz-Vesper, PhD

• Maecker-Kolhoff, Britta, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Britta Maecker-Kolhoff, MD

• Hinze, Christian, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Christian Hinze, DrMed, MD

Background

Refractory BK virus nephropathy (BKVNP) is a significant risk factor for graft loss in kidney transplant recipients. Currently, there are no targeted therapies available for BKVNP. Given the importance of cellular immunity in viral clearance, we investigated the effects of allogeneic BK virus-specific T cell transfer on graft function, BKV-specific T cell levels, and BKV replication in patients’ blood.

Methods

We included three kidney transplant recipients with refractory BKVNP. Refractory BKVNP was defined by persistent BKV replication (>1000 IU/ml), minimum possible immunosuppression, low BKV-specific T cell levels, and histologic evidence of BKVNP. For two patients, donors for virus-specific T cells were selected from the third party T cell donor registry (alloCELL), ensuring the best possible HLA compatibility with the transplanted organ and the recipient. For one patient, the related living organ donor was selected, thus resulting in a haploidentical T cell transfer. BKV-specific T cells were produced from leukapheresis, short-term stimulation with LT and VP1 overlapping peptide pools, followed by cytokine selection and magnetic separation. Patients received at least four T cell transfusions (first fresh, subsequent cryopreserved) every three weeks. BKV load was quantified by qPCR, and BKV-specific T cells were enumerated using interferon-γ Elispot assay.

Results

We observed significant declines in BKV load in all cases (93.16%, 78.10%, 71.11% decrease compared to pre-therapy levels), along with significant increases in BKV-specific T cells in recipients’ blood. The most pronounced reduction in BKV load (93.16%) was observed in the haploidentical transplant patient, emphasizing the relevance of HLA compatibility to ensure an adequate T-cell milieu. Graft function remained stable throughout therapy, and no infusion-related adverse events were observed.

Conclusion

Allogeneic BK virus-specific T cell therapy shows promise in treating refractory BKVNP in kidney transplant recipients. Patient selection based on BKV-specific T cell levels, BKV blood levels, graft function, and histology is essential. Further evaluation is needed to determine its clinical efficacy.