@article{RoyLachanceCohenetal.2019,
  author    = {Roy, Denis Claude and Lachance, Sylvie and Cohen, Sandra and Delisle, Jean-S{\´e}bastien and Kiss, Thomas and Sauvageau, Guy and Busque, Lambert and Ahmad, Imran and Bernard, Lea and Bambace, Nadia and Boum{\´e}dine, Radia S. and Guertin, Marie-Claude and Rezvani, Katayoun and Mielke, Stephan and Perreault, Claude and Roy, Jean},
  title     = {Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis},
  series = {British Journal of Haematology},
  volume    = {186},
  journal   = {British Journal of Haematology},
  number    = {5},
  doi       = {10.1111/bjh.15970},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227075},
  pages     = {754-766},
  year      = {2019},
  abstract  = {Graft-versus-host disease (GVHD) is a major cause of transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T-cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant risks, particularly infections and relapse, compromising survival. A photodepletion strategy to eliminate alloreactive T cells from mismatched donor lymphocyte infusions (enabling administration without immunosuppression), was used to develop ATIR101, an adjunctive therapy for use after haploidentical HSCT. In this phase I dose-finding study, 19 adults (median age: 54 years) with high-risk haematological malignancies were treated with T-cell-depleted human leucocyte antigen-haploidentical myeloablative HSCT followed by ATIR101 at doses of 1 x 10(4)-5 x 10(6) CD3(+) cells/kg (median 31 days post-transplant). No patient received post-transplant immunosuppression or developed grade III/IV acute GVHD, demonstrating the feasibility of ATIR101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long-term follow -up of patients treated with ATIR101 in this study. At 1 year, all 9 patients receiving doses of 0 center dot 3-2 x 10(6) CD3(+) cells/kg ATIR101 remained free of serious infections and after more than 8 years, TRM was 0\%, relapse-related mortality was 33\% and overall survival was 67\% in these patients.},
  language  = {en}
}
@article{StringarisSekineKhoderetal.2014,
  author    = {Stringaris, Kate and Sekine, Takuya and Khoder, Ahmad and Alsuliman, Abdullah and Razzaghi, Bonni and Sargeant, Ruhena and Pavlu, Jiri and Brisley, Gill and de Lavallade, Hugues and Sarvaria, Anushruthi and Sarvaria, Anushruthi and Mielke, Stephan and Apperley, Jane F. and Shpall, Elisabeth J. and Barrett, A. John and Rezvani, Katayoun},
  title     = {Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia},
  series = {Haematologica},
  volume    = {99},
  journal   = {Haematologica},
  number    = {5},
  issn      = {1592-8721},
  doi       = {10.3324/haematol.2013.087536},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116550},
  pages     = {836-847},
  year      = {2014},
  abstract  = {The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-alpha and IFN-gamma production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-alpha production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-alpha and IFN-gamma production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival.},
  language  = {en}
}