{"id":{"repo_id":"radboud","oai_identifier":"oai:repository.ubn.ru.nl:2066/30117"},"canonical_url":"https://search.dev.ndltd.org/etd/radboud/oai:repository.ubn.ru.nl:2066/30117","repository":{"repo_id":"radboud","name":"Radboud University Nijmegen","base_url":"https://repository.ubn.ru.nl/oai/request"},"display":{"title":"Characterization of leukemia - associated minor histocompatibility antigens as targets in anti-leukemic immunotherapy.","abstract":"Contains fulltext : 30117_charoflea.pdf (Publisher’s version ) (Open Access)","abstract_html":"Contains fulltext : 30117_charoflea.pdf (Publisher’s version ) (Open Access)","abstract_has_math":false,"creators":["Rijke, B. de"],"institution":"S.l. : s.n.","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Witte, T.J.M. de","Dolstra, H.","Wiel-van Kemenade, E. van de"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007","date_published":"2007","updated_at":"2026-07-24T04:02:27Z","subjects":["UMCN 1.2: Molecular diagnosis, prognosis and monitoring"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2066/53177","9789090237442"],"render_values":[{"text":"http://hdl.handle.net/2066/53177","href":"http://hdl.handle.net/2066/53177","code":true},{"text":"9789090237442","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2066/30117","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Witte, T.J.M. de","Dolstra, H.","Wiel-van Kemenade, E. van de"]},{"key":"dc:creator","label":"Author","values":["Rijke, B. de"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2007"]},{"key":"dc:publisher","label":"Institution","values":["S.l. : s.n."]},{"key":"dc:type","label":"Dc Type","values":["Doctoral thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["UMCN 1.2: Molecular diagnosis, prognosis and monitoring"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://repository.ubn.ru.nl//bitstream/handle/2066/30117/30117_charoflea.pdf","http://hdl.handle.net/2066/30117","http://hdl.handle.net/2066/53177","9789090237442"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Contains fulltext : 30117_charoflea.pdf (Publisher’s version ) (Open Access)","This thesis describes the characterization and identification of CTL-defined leukemia-associated minor histocompatibility antigens (mHAg) for the development of novel cellular immunotherapeutic approaches to successfully treat patients with relapsed hematopoietic malignancies after allogeneic stem cell transplantation (SCT). Previously, a leukemia-associated mHAg, HB-1, was identified. Expression analysis showed restricted HB-1 gene expression in B-ALL and Epstein-Barr virus-transformed B cells. Therefore, additional studies were conducted to provide information regarding its potency as a T cell target for cellular immunotherapy. Experimental data indicated that mHAg HB-1 can induce bi-directional CTL responses. Furthermore, TCR-specificity analysis of HB-1 peptide variant-specific CTL revealed that differential recognition o is the result of TCR discrimination. In addition, the potential use of the HB-1 antigen as an autologous T cell target for immunotherapy was investigated. In vitro CTL induction experiments resulted in the generation of autologous cytotoxic and helper T cell responses against the HB-1 antigen. Furthermore, a novel human mHAg, LRH-1, was molecular identified. The immunogenicity for LRH-1 is due to differential protein expression between recipient and donor as a result of a homozygous frameshift polymorphism in the P2X5 gene. Expression analysis of P2X5 showed selective expression in leukemic and normal CD34+ progenitor cells, lymphoid cells, lymphoid tissues and in tumor cells from all stages of lymphoid development. Furthermore, a clear correlation between the emergence of CTL and complete remission of the CML was demonstrated. mHAg HB-1 and LRH-1 represent potent antigens to induce specific GVL reactivity in a significant number of patients in the setting of mHAg-based immunotherapy. The studies described in this thesis provide novel insights and perspectives in mHAg immunobiology. In the future, this knowledge provides a solid basis for the development of specific cellular immunotherapeutic strategies to successfully treat patients with relapsed hematopoietic malignancies after allogeneic SCT","RU Radboud Universiteit Nijmegen, 24 januari 2007","Promotor : Witte, T.J.M. de Co-promotores : Dolstra, H., Wiel-van Kemenade, E. van de","149 p."]},{"key":"dc:title","label":"Title","values":["Characterization of leukemia - associated minor histocompatibility antigens as targets in anti-leukemic immunotherapy."]}]}],"canonical_facts":{"dc:contributor":["Witte, T.J.M. de","Dolstra, H.","Wiel-van Kemenade, E. van de"],"dc:creator":["Rijke, B. de"],"dc:date":["2007"],"dc:description":["Contains fulltext : 30117_charoflea.pdf (Publisher’s version ) (Open Access)","This thesis describes the characterization and identification of CTL-defined leukemia-associated minor histocompatibility antigens (mHAg) for the development of novel cellular immunotherapeutic approaches to successfully treat patients with relapsed hematopoietic malignancies after allogeneic stem cell transplantation (SCT). Previously, a leukemia-associated mHAg, HB-1, was identified. Expression analysis showed restricted HB-1 gene expression in B-ALL and Epstein-Barr virus-transformed B cells. Therefore, additional studies were conducted to provide information regarding its potency as a T cell target for cellular immunotherapy. Experimental data indicated that mHAg HB-1 can induce bi-directional CTL responses. Furthermore, TCR-specificity analysis of HB-1 peptide variant-specific CTL revealed that differential recognition o is the result of TCR discrimination. In addition, the potential use of the HB-1 antigen as an autologous T cell target for immunotherapy was investigated. In vitro CTL induction experiments resulted in the generation of autologous cytotoxic and helper T cell responses against the HB-1 antigen. Furthermore, a novel human mHAg, LRH-1, was molecular identified. The immunogenicity for LRH-1 is due to differential protein expression between recipient and donor as a result of a homozygous frameshift polymorphism in the P2X5 gene. Expression analysis of P2X5 showed selective expression in leukemic and normal CD34+ progenitor cells, lymphoid cells, lymphoid tissues and in tumor cells from all stages of lymphoid development. Furthermore, a clear correlation between the emergence of CTL and complete remission of the CML was demonstrated. mHAg HB-1 and LRH-1 represent potent antigens to induce specific GVL reactivity in a significant number of patients in the setting of mHAg-based immunotherapy. The studies described in this thesis provide novel insights and perspectives in mHAg immunobiology. 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