Date: Saturday, June 11, 2016
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Halls C&D
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).
To cite this abstract in AMA style:Lamarche C, Julie O, Carli C, Delisle J-S. Autologous BK-Specific T-Cell Lines in Kidney Transplant Recipients. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/autologous-bk-specific-t-cell-lines-in-kidney-transplant-recipients/. Accessed March 1, 2021.
« Back to 2016 American Transplant Congress