Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors

BACKGROUND: Adoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications. METHODS: We provide results of a personalized T-cell manufacturing program evaluating donor, patient, T-cell product and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T-lymphocyte (EBV-CTL) products from stem cell donors (SCD), related third party donors (TPD) or unrelated TPD from the allogeneic T-cell donor registry (alloCELL) established at Hannover Medical School were manufactured by immunomagnetic selection using CliniMACS Plus or Prodigy device and EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated and patient outcome and side effects were retrieved by retrospective chart analysis. RESULTS: Forty clinical-grade EBV-CTL products from SCDs, related or unrelated TPDs were generated for 37 patients with and without transplantation (Tx) history within 5 days (median) after donor identification. 34 patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients' blood were detectable in 16/18 monitored patients (89 %) after transfer and correlated with clinical response. CONCLUSION: In conclusion, personalized clinical-grade manufacturing of EBV-CTL products via immunomagnetic selection from SCD, related or unrelated TPD is feasible in a timely manner. Overall, EBV-CTL were clinically effective and well-tolerated. Our data suggest EBV-CTL as promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT as well as patients with pre-existing organ dysfunction

metal-dependent versatility of the oxidation state and related co oxidation performance of noble metal nanoparticles in interaction with ceria

SSCI-VIDE+ATARI:ECI2D:ING+LPI:TSN:FMO:GPOInternational audienceDue to its excellent redox properties, ceria is extensively used in heterogeneous catalysis, where it can act as an oxygen buffer in oxidation reactions or prevent coking of metal phases in hydrocarbon reforming reactions. In this work, ceria-supported platinum-group metal (Pt, Pd, Ir, Rh, Ru) nanoparticles were prepared in a single step by solution combustion synthesis, a simple and inexpensive method favoring metal-oxide interaction and thermal stability [1-3]. The powders were characterized by a variety of techniques (HRTEM, SEM, XRD, XPS, Raman spectroscopy, etc.) and systematically compared for CO oxidation and preferential CO oxidation in excess of hydrogen (PROX) in a flow-fixed-bed reactor. Ceria-supported Rh and Pt appear as the most efficient catalysts in CO oxidation (CO:O2 = 2:2 mol% of 1 atm) and PROX (CO:O2:H2 = 2:2:48 mol%), respectively [3]. These two systems, as well as pristine ceria, were further selected for a comparative operando DRIFTS-MS study, with particular focus on the effect of CO+O2 conditions on the nature of the adsorbed species. Whereas the reaction starts above 150 °C on CeO2 and RhâCeO2, and does not depend on the state of the surface (i.e. pre-exposed to CO:O2 4:4 mol% or 7:1 mol% mixture), PtâCeO2 shows strong dependency on the initial state and substantial activity is achieved at much lower temperatures with the CO-rich feed. On the basis of IR data, this result was related to a change in Pt oxidation state via strong interaction with ceria [4].[1]T.S. Nguyen et al., J. Mater. Chem. A 2, 19822 (2014).[2]G. Postole et al., Appl. Catal. B 166-167, 580 (2015).[3]T.S. Nguyen et al., Catal. Today 253, 106 (2015).[4]A. Kaftan et al., Catal. Sci. Technol., in press (DOI: 10.1039/c5cy00827a

Dissecting Epstein-Barr virus-specific T-cell responses after allogeneic EBV-specific T-cell transfer for central nervous system posttransplant lymphoproliferative disease

Epstein–Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) with central nervous system (CNS) involvement is a severe complication after solid organ transplantation. Standard treatment with reduction of immunosuppression and anti-CD20 antibody application often fails leading to poor outcome. Here, we report the case of an 11-year-old boy with multilocular EBV-positive CNS PTLD 10 years after liver transplantation. Complete remission was achieved by repeated intravenous and intrathecal anti-CD20 antibody rituximab administration combined with intrathecal chemotherapy (methotrexate, cytarabine, prednisone) over a time period of 3 months. Due to the poor prognosis of CNS PTLD and lack of EBV-specific T-cells (EBV-CTLs) in patient’s blood, we decided to perform EBV-directed T-cell immunotherapy as a consolidating treatment. The patient received five infusions of allogeneic EBV-CTLs from a 5/10 HLA-matched unrelated third-party donor. No relevant acute toxicity was observed. EBV-CTLs became detectable after first injection and increased during the treatment course. Next-generation sequencing (NGS) TCR-profiling verified the persistence and expansion of donor-derived EBV-specific clones. After two transfers, epitope spreading to unrelated EBV antigens occurred suggesting onset of endogenous T-cell production, which was supported by detection of recipient-derived clones in NGS TCR-profiling. Continuous complete remission was confirmed 27 months after initial diagnosis