Utilisation de lymphocytes T en thérapie cellulaire pour le traitement de la néphropathie au polyomavirus BK chez les greffés rénaux
More than 75% of the population has been exposed to BK polyomavirus and carries latent virus in the uroepithelium without any complications. However, it can reactivates in kidney transplant recipients (KTR) and lead to a nephropathy affecting graft survival. Recipient anti-viral immunity is the cornerstone of BK-virus associated nephropathy prevention and treatment and thus, reduction of immunosuppression is the only well-accepted treatment. Adoptive immunotherapy is a promising solution to this problem, allowing a specific T cell mediated response against this virus without the alloreactive risk. It was demonstrated efficacious for other viral infections in immunocompromised hosts but it has not been used in this specific context. Our objective was to adapt and validate a clinical-compliant protocol to obtain BK-specific T cell lines from viremic KTR and to compare their expansion, differentiation and specificity to ones obtained from healthy donors. Although comparable specificity and differentiation status, cell expansions form KTR were not systematically sufficient for a therapeutic dose. The addition of a stimulation with dendritic cells improved cell expansion in addition to favors a central memory phenotype and refined BKspecificity. Despite polyclonality, T cell lines didn’t demonstrated alloreactivity in a chromium release assay and in vivo. Furthermore, T cell lines could persist and proliferates in vivo. This protocol is ready for a phase I/II clinical trial. This opens the possibility to solve the current conundrum and treat PVAN without increasing rejection risk.
BK polyomavirus Kidney transplant Cellular therapy Immunotherapy Polyomavirus-associated nephropathy