Browsing by Author "Dave, Hema"

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    Safety and feasibility of virus-specific T cells derived from umbilical cord blood in cord blood transplant recipients
    (American Society of Hematology, 2019-07-23) Abraham, Allistair A.; John, Tami D.; Keller, Michael D.; Cruz, C. Russell N.; Salem, Baheyeldin; Roesch, Lauren; Liu, Hao; Hoq, Fahmida; Grilley, Bambi J.; Gee, Adrian P.; Dave, Hema; Jacobsohn, David A.; Krance, Robert A.; Shpall, Elizabeth. J.; Martinez, Caridad A.; Hanley, Patrick J.; Bollard, Catherine M.; Biostatistics, IU School of Medicine
    Adoptive transfer of virus-specific T cells (VSTs) has been shown to be safe and effective in stem cell transplant recipients. However, the lack of virus-experienced T cells in donor cord blood (CB) has prevented the development of ex vivo expanded donor-derived VSTs for recipients of this stem cell source. Here we evaluated the feasibility and safety of ex vivo expansion of CB T cells from the 20% fraction of the CB unit in pediatric patients receiving a single CB transplant (CBT). In 2 clinical trials conducted at 2 separate sites, we manufactured CB-derived multivirus-specific T cells (CB-VSTs) targeting Epstein-Barr virus (EBV), adenovirus, and cytomegalovirus (CMV) for 18 (86%) of 21 patients demonstrating feasibility. Manufacturing for 2 CB-VSTs failed to meet lot release because of insufficient cell recovery, and there was 1 sterility breach during separation of the frozen 20% fraction. Delayed engraftment was not observed in patients who received the remaining 80% fraction for the primary CBT. There was no grade 3 to 4 acute graft-versus-host disease (GVHD) associated with the infusion of CB-VSTs. None of the 7 patients who received CB-VSTs as prophylaxis developed end-organ disease from CMV, EBV, or adenovirus. In 7 patients receiving CB-VSTs for viral reactivation or infection, only 1 patient developed end-organ viral disease, which was in an immune privileged site (CMV retinitis) and occurred after steroid therapy for GVHD. Finally, we demonstrated the long-term persistence of adoptively transferred CB-VSTs using T-cell receptor-Vβ clonotype tracking, suggesting that CB-VSTs are a feasible addition to antiviral pharmacotherapy.