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Related Experiment Video

Updated: May 15, 2025

Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry

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Published on: July 13, 2019

Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy.

Maud Wilhelm¹, Amandeep Kaur, Anne Geng

¹Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.

Transplantation

|April 9, 2025

Summary

This summary is machine-generated.

Optimizing ex vivo expansion of BK polyomavirus-specific T cells using G-Rex cultures enhances cell counts and cytotoxicity. Immune checkpoint inhibitors like pembrolizumab can improve T-cell function and overcome donor variability in adoptive cell therapy for BKPyV nephropathy.

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Area of Science:

Immunology
Transplantation Medicine
Cell Therapy

Background:

BK polyomavirus (BKPyV) nephropathy is a leading cause of kidney transplant failure.
Current treatments focus on reducing immunosuppression to restore BKPyV-specific immunity.
Ex vivo expanded T cells offer potential but have suboptimal efficacy due to donor variability.

Purpose of the Study:

To optimize ex vivo expansion protocols for BKPyV-specific T cells.
To compare conventional and G-Rex culture systems for T-cell expansion.
To assess the impact of immune checkpoint inhibitors on T-cell function.

Main Methods:

Compared conventional and G-Rex expansion cultures for BKPyV-specific T cells.
Stimulated T cells with BKPyV peptide pools and assessed cytokine/cytotoxic responses.
Evaluated programmed cell death protein 1 (PD-1) and PD-1 ligand 1 (PD-1L) expression.
Assessed the effect of pembrolizumab on T-cell responses and cytotoxicity.

Main Results:

G-Rex cultures yielded higher cell counts than conventional cultures.
Expanded T cells demonstrated polyfunctional cytokine production and cytotoxicity against BKPyV-infected cells.
G-Rex-expanded T cells showed increased PD-1 expression.
Pembrolizumab reduced PD-1 expression, enhanced T-cell responses, and increased cytotoxicity.

Conclusions:

Upregulated PD-1 on ex vivo expanded T cells contributes to donor variability and may limit adoptive cell therapy efficacy.
BKPyV-infected renal proximal tubule epithelial cells (RPTECs) upregulate PD-L1 under inflammatory conditions.
Ex vivo addition of immune checkpoint inhibitors warrants evaluation to enhance BKPyV-specific T-cell therapy for kidney transplant patients.