Safe adoptive transfer of virus‐specific T‐cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specificT-cells or chimeric-antigen receptor T-cells which are reviewed in this study.

Section: Infectionmentioning

confidence: 99%

Umbilical cord blood graft engineering: challenges and opportunities

Thompson

Rezvani

Hosing

et al. 2015

“…49,50 An algorithm for treatment of ADV infections has been reviewed in detail by Feuchtinger et al 51 Low numbers of specific T cells were isolated after ex vivo stimulation by IFN-g secretion and magnetic microbeads and administered without inducing GVHD. 52 Outcome and future perspectives Transplant related mortality could be effectively reduced by improved T cell recovery and close monitoring of viral loads followed by preemptive therapy and by the use of reduced-intensity conditionings, whereas relapse remains the major cause of death. 53 3y-EFS in single center studies with CD34 þ selected grafts were 36 and 48% for ALL (CR1-3) and 18 and 28% for myeloic leukemias (CR1-2); 11,13 a recent collaborative retrospective study showed 3y-EFS of 35% (CR1), 28% (CR2) and 0% (CR3) in patients with ALL.…”

Section: Immune Reconstitution and Trmmentioning

confidence: 99%

Haploidentical SCT in children: an update and future perspectives

Lang

Handgretinger

2008

Transplantation of haploidentical stem cells has become a well-established approach, which makes a potential donor available for almost all patients. This review focuses on current results and new strategies, especially in pediatric patients with malignant diseases. CD34 þ positive selection was the most common procedure for graft manipulation in the past years, whereas T and B cell depletion is a promising new method. GVHD could herewith be effectively reduced and primary engraftment was reported in 83-100% of patients after transplantation of high stem cell doses. For patients with ALL in remission, diseasefree survival at 3 years ranged between 22 and 48%. TRM, mainly because of viral infections, was improved by the use of reduced-intensity conditioning (which helped to speed up T cell recovery) and by close monitoring of viral loads and prophylactic/preemptive therapy. The role of donor-derived Ag-specific T cells against viral and fungal antigens is currently under investigation. Patients with active disease at the time of transplantation had a poor outcome and several attempts to improve these results are currently evaluated, such as co-infusion of natural killer cells, co-transplantation of MSC, use of new antileukemic drugs and post-transplant immunotherapy.

“…16 For this reason, immunotherapy with donor T cells has been suggested, and a novel approach using purified AdV-specific donor T cells is promising, although in need of further evaluation. 17 At present, surveillance of AdV infection after HSCT is not routinely implemented, although the technology of choice, quantitative PCR, is widely available. The possible advantages are that such surveillance programs facilitate early detection and intervention and promote preemptive treatment before symptoms emerge.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Öhrmalm

Lindblom

Omar

et al. 2010

Adenoviruses (AdV) have emerged as important causes of morbidity and mortality in patients after hematopoietic SCT (HSCT). Early diagnosis of the infection by detection of viral DNA may improve the prognosis. A surveillance strategy was evaluated for detection of AdV DNA by PCR in a prospective study of unselected allogeneic HSCT recipients. In parallel with a routine CMV surveillance program, plasma from 20 children and 77 adults was analyzed by quantitative PCR for detection of AdV DNA. In addition, in 12 unselected patients, the presence of AdV-specific T cells were analyzed by enzyme-linked immunosorbent spot (ELISPOT) at 1 to 3 months after transplantation. A total of 5 of 97 (5%) patients had detectable AdV DNA in peripheral blood. Only one patient had high titers and none developed AdV disease. BM as a source of stem cells and myelodysplastic syndrome as the indication for transplantation were independently associated with higher risk of acquiring AdV infection. AdV-specific T cells were detected in 7 (58%) of 12 patients. Although AdV DNA was found in peripheral blood by quantitative PCR in 5% of patients undergoing allogeneic HSCT, the present surveillance program did not have a significant effect on the clinical outcome.