Background: More than 75% of the population has been exposed to BK polyomavirus and carries latent virus in the uroepithelium. Immunocompetent hosts are asymptomatic but reactivations in immunocompromised kidney transplant recipients can lead to polyomavirus-associated nephropathy in up to 10% of them, thereby affecting graft survival. To date, reduction of immunosuppression is the most accepted strategy to treat BK-related complications but has the disadvantage of increasing rejection risk by non-specifically increasing immune competence. This nonetheless indicates that the recipient anti-viral immunity is the cornerstone of PVAN prevention and treatment. The objective of this study was to obtain clinical grade BK-specific T-cell lines from viremic transplant recipients for future adoptive immunotherapy.

Methods: We developed and compared two protocols to obtain BK-specific T cells lines from BK-viremic kidney transplant recipients. We used 15×10⁶ peripheral blood mononuclear cells pulsed with two BK-specific peptide libraries, with or without monocytes-derived dendritic cells. At the end of the 14-days culture, we performed cell count, flux cytometry analysis, enzyme-linked immunospots (ELISpot) and chromium⁵¹ cytotoxicity assays.

Results: We successfully produced BK-specific T-cell lines from kidney transplant recipients. At the end of the culture, more than 150 x10⁶ cells were obtained, which is sufficient for multiple infusions based on recent adoptive immunotherapy trials in other clinical settings (estimated at up to 20-40 x10⁶/m²). T-cell lines are BK-specific, as seen by the ELISpot and chromium cytotoxicity assays. However, compared to healthy donors, dendritic cells stimulation is necessary in kidney transplant recipients in order to obtain comparable T-cell expansion. In addition, antigen presentation through dendritic cells favors T-cell early memory differentiation, which could potentiate the therapeutic response after an adoptive transfer.

Conclusion: In kidney transplant recipients, it is possible to obtain clinical grade anti-BK T cell lines at a clinical scale level for adoptive immunotherapy.This opens the possibility to solve the current conundrum and treat PVAN without increasing rejection risk.

CITATION INFORMATION: Lamarche C, Julie O, Carli C, Delisle J.-S. Autologous BK-Specific T-Cell Lines in Kidney Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).

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