In the context of haploidentical hematopoietic stem cell transplantation (HSCT) followed by a post-transplant cyclophosphamide treatment (PT/Cy), we aim at tracking alloreactive-T cells at the time of the GVHD. Indeed, we suspect that Tscm, which escaped the PT/Cy action, gave raise to T-cells aggressive clones. Using a TCR-finger print strategy, we are evaluating the relationship between alloreactive-T cells at the time of the GVHD and T-cells subsets contained in the graft prior the transplantation. We are evaluating and developing new strategies to control the reactivation of Tscm cells and are validating our approach in the Humanized rodent platform.
The human Cytomegalovirus (HCMV) is a widely-spread virus. The primary infection is mainly asymptomatic but the virus persists lifelong in blood progenitor cells. In recipient of hematopoietic stem cell transplantation, HCMV is the major cause of transplant-related mortality. Indeed, the immunosuppressive regime and the leucopenia following HSCT impair the immune response against HCMV and this can lead to severe end-organ diseases and mortality. We used CRISRP-Cas9 system to unsettle the human Cytomegalovirus genome. In vitro, we show that CRIPSR-Cas9 anti-HCMV, delivered by lentiviral vectors, disrupts CMV genome, blocks viral protein expression and viral replication. We are now validating this strategy in latently infected cells.