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Dr. Harry Dolstra
Research interests include immune regulation and modulation of the graft-versus-tumor responses induced after allogeneic hematopoietic stem cell transplantation. Major topics include investigation of the molecular identity and immunological role of minor histocompatibility antigens in inducing alloreactive T cell responses, the role of dendritic cells (DC) in activating and orchestrating the migratory behavior of alloreactive T cells and delineating the involvement of co-signaling pathways in alloreactive T cell function. In addition to the more fundamental investigations, novel cellular immunotherapeutic strategies are being explored for the treatment of patients with hematological cancers. Current projects include the clinical use of T cell transfer, DC-based vaccines and alloreactive NK cell products for transplant-related immunotherapy. |
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Recent key publications Norde WJ, Overes IM, Maas F, Vos JCM, Fredrix H, Kester MGD, van der Voort R, Jedema I, Falkenburg JHF, Schattenberg AV, de Witte.TM, Dolstra H. Myeloid leukemic progenitor cells can be specifically targeted by minor histocompatibility antigen LRH-1-reactive cytotoxic T cells. Blood 2008, Dec 12 Spaapen RM, Lokhorst HM, van den Oudenalder K, Otterud BE, Dolstra H, Leppert MF, Minnema MC, Bloem AC, Mutis T. Towards targeting B cell cancers with CD4+ CTLs: a novel polymorphic antigen on CD19 identified by a powerful genetic strategy. J Exp Med 2008, 205:2863-2872. Spierings E, Hendriks M, Absi L, Canossi A, Chhaya S, Crowley J, Dolstra H, Eliaou JF, Ellis T, Enczmann J, Fasano ME, Gervais T, Gorodezky C, Kircher B, Laurin D, Leffell MS, Loiseau P, Malkki M, Markiewicz M, Martinetti M, Maruya E, Mehra N, Oguz F, Oudshoorn M, Pereira N, Rani R, Sergeant R, Thomson J, Tran TH, Turpeinen H, Yang KL, Zunec R, Carrington M, de Knijff P, Goulmy E. Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations. Plos Genetics 2007, 3: 1108-1119. De Rijke B, van Horssen-Zoetbrood A, Beekman J, Otterud B, Maas F, Woestenenk R, Kester M, Leppert M, Schattenberg A, De Witte T, Van de Wiel-van Kemenade E, Dolstra H. A frame-shift polymorphism in the P2X5 gene elicits an allogeneic CTL response associated with remission of chronic myeloid leukemia. J Clin Invest 2005, 115: 3506-3516. De Rijke B, Fredrix H, Zoetbrood A, Scherpen F, Witteveen H, De Witte T, Van de Wiel-van Kemenade E, Dolstra H. Generation of autologous cytotoxic and helper T cell responses against the B cell leukemia-assocciated antigen HB-1: relevance for precursor-B-ALL-specific immunotherapy. Blood 2003, 102: 2885-2891. |
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