HLA-matched allogeneic stem cell transplantation (alloSCT) is a potential curative therapy for patients with high-risk hematologic malignancies. The therapeutic effect of alloSCT is mediated by T... Show moreHLA-matched allogeneic stem cell transplantation (alloSCT) is a potential curative therapy for patients with high-risk hematologic malignancies. The therapeutic effect of alloSCT is mediated by T cells derived from the stem cell donor that have the potential to recognize and eliminate malignant cells of patient origin, better known as the graft-versus-leukemia effect. Besides, donor-derived T cells are of importance for the protection against viruses early after alloSCT. On the other hand, T cells of donor origin can also initiate harmful graft-versus-host disease if healthy cells of the patient are recognized. Therefore, the major challenge in the field of alloSCT is to find a balance between graft-versus-leukemia effect and viral protection versus graft-versus-host disease with the aim to reduce complications early after alloSCT. In this thesis, the manipulation of donor-derived T cells at different stages during the process of HLA-matched alloSCT was investigated: from in vitro T-cell depletion of the graft before infusion into the patient until adoptive T-cell therapy early after alloSCT to support anti-viral immunity and graft-versus-leukemia effect. Show less
Alemtuzumab (ALM) is a cytotoxic monoclonal antibody that is used as a therapeutic agent in a variety of clinical settings. The target antigen for ALM is CD52, which is highly expressed on the... Show moreAlemtuzumab (ALM) is a cytotoxic monoclonal antibody that is used as a therapeutic agent in a variety of clinical settings. The target antigen for ALM is CD52, which is highly expressed on the membrane of mature lymphocytes, but not or only marginally on hematopoietic stem cells, red blood cells, and non-hematopoietic tissues. As such, ALM can be administered for the purpose of lymphocyte depletion with no or only minimal toxicity to other tissues. In this thesis, the mechanism of action of ALM was investigated in the context of two clinical settings, i.e. T-cell depletion before allogeneic stem cell transplantation (alloSCT) and depletion of malignant cells in B lymphoblastic leukemia (B-ALL). Show less
