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| 2. |
- Arruda, Lucas C. M., et al.
(author)
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A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells in vitro and in vivo
- 2022
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 107:8, s. 1786-1795
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Journal article (peer-reviewed)abstract
- Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34(+) blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34(+)CD38(-) phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo. Our results show that this CD34-specific BTE induces CD34-dependent T-cell activation and subsequent leukemia cell killing in a dose-dependent manner, further corroborated by enhanced T-cell-mediated killing at the singlecell level. Additionally, the BTE triggered efficient T-cell-mediated depletion of CD34(+) hematopoietic stem cells from peripheral blood stem cell grafts and CD34(+) blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BTE had in vivo efficacy by depleting CD34(+) blasts and leukemic stem cells without side effects. Taken together, these data demonstrate that the CD34-specific BTE has robust antitumor effects, supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes.
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| 3. |
- Kremer, A. N., et al.
(author)
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Development of a coordinated allo T cell and auto B cell response against autosomal PTK2B after allogeneic hematopoietic stem cell transplantation
- 2014
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 99:2, s. 365-369
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Journal article (peer-reviewed)abstract
- It is well known that allo-reactive T cells play a crucial role in graft-versus-leukemia and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (alloSCT). Allo-reactive CD4+ T cells can mediate direct cytolysis, but may also stimulate production of IgG antibodies as helper cells. Immune complexes may subsequently be processed and presented by professional antigen presenting cells and stimulate induction of specific CD8+ T cells. As such, proteins targeted in coordinated T- and B-cell responses may represent a class of immunodominant antigens in clinical responses after alloSCT. We previously identified LB-PTK2B-1T as HLA class II restricted polymorphic antigen in a patient treated with donor lymphocyte infusion for relapsed chronic myeloid leukemia after HLA-matched alloSCT. Since PTK2B has also been described as antibody target, we here investigated whether a coordinated T- and B-cell response against PTK2B was induced. Patient serum before and after alloSCT and donor lymphocyte infusion (DLI) was screened for antibodies, and we indeed observed development of a humoral immune response against PTK2B. Antibodies against PTK2B were only found after DLI and, in contrast to the CD4+ T cells, recognized a monomorphic region of the protein. To our knowledge, this is the first description of a coordinated allo-reactive CD4+ T-cell and auto-reactive antibody response against an autosomal antigen.
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| 5. |
- Liwing, J., et al.
(author)
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Is multiple myeloma a chronic disease?
- 2012
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In: Haematologica. - : Fondazione Ferrata Storti. - 0390-6078 .- 1592-8721. ; 97, s. 345-346
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Journal article (other academic/artistic)
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| 6. |
- Nilsson, Björn, et al.
(author)
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Cross-platform classification in microarray-based leukemia diagnostics
- 2006
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In: Haematologica. - 1592-8721 .- 0390-6078. ; 91:6, s. 821-824
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Journal article (peer-reviewed)abstract
- Gene expression profiling is a powerful technique for classifying hematologic malignancies. Its clinical use is, however, currently hindered by the need to collect large sets of expression profiles at each diagnostic facility. To overcome this limitation, we introduced cross-platform classification, allowing classifier construction using pre-existing microarray datasets. As proof-of-principle, we performed cross-platform classification of acute myeloid leukemia and childhood acute lymphoblastic leukemia using expression data from four different facilities. We show that cross-platform classification of these disorders is achievable, and, strikingly, that the diagnostic accuracy can be retained. We conclude that cross-platform classification constitutes an effective and convenient way to implement microarray diagnostics.
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