Board of examiners Prof. Steven Pals Department of Pathology, University of Amsterdam The Netherlands PhD in Medical Sciences 2014-2015 Prof. Michel Delforge Department of Hematology KU Leuven INVITATION to the Public defence of Prof. Jo Van Ginderachter Haneen NUR Laboratory of Cellular and Molecular Immunology Vrije Universiteit Brussel Dr. Brenda De Keersmaecker To obtain the academic degree of ‘DOCTOR IN MEDICAL SCIENCES’ Laboratory of Molecular and Cellular Therapy Biological and clinical implications of invariant natural Vrije Universiteit Brussel killer T cells in multiple myeloma: rising the potential for Prof. Ivan Van Riet, Chair immunotherapy Stem Cell Laboratory Clinical Hematology UZ Brussel Vrije Universiteit Brussel Wednesday 17 September 2014 Auditorium Brouwer, 17:00 Faculty of Medicine and Pharmacy, Laarbeeklaan 103, 1090 Brussel Prof. Karin Vanderkerken and Prof Eline Menu, Promotors Hematology and Immunology Department of Biomedical Sciences Vrije Universiteit Brussel How to reach the campus Jette: http://www.vub.ac.be/english/infoabout/campuses Summary of the dissertation Curriculum Vitae Invariant natural killer T cells (iNKTs) are a small subset of T cells Haneen Nur was born on 05/09/1969 in Amman, Jordan. Before 1990 expressing a unique T cell receptor. They can be activated by αGalactosylceramide (α-GalCer) glycolipid represented by antigen- presenting cells. As a consequence, they rapidly produce Th1 cytokines such as IFN-γ, which in turn augments their responses against cancers she lived in Kuwait where she started her Bachelor study in Microbiology at Kuwait University. Unfortunately, the Gulf war broke out in 1990 so she moved with her family to Jordan. She could not finish her study, and e.g. multiple myeloma (MM). Unfortunately, iNKTs become anergic in that was a real challenge in her life. She struggled to obtain the Bachelor progressive MM with a functional deficiency. degree in Biological Sciences from Jordan University, and in 1993 she In this thesis we first evaluated iNKTs and described their number and obtained the degree with a high distinction. She worked as a lecturer in activity in the 5T33MM model. We found a dramatic drop in their Al-Quds College, then in the Applied Science University as a teaching numbers at the end stage of the disease. This was consistent to the number of circulating iNKTs in MM patients at relapse. We also demonstrated that the decline in iNKT number led to a deficiency in IFN- assistant in the biomedical labs to save money for her Master study. In 1997, she graduated and obtained her master degree in Biological γ secretion. In addition, we found that injection of α-GalCer loaded Sciences from Jordan University. In the same year, she moved to the dendritic cells (DCs) in 5T33MM mice prolonged their survival. West Bank/ Palestine. In 1998, she joined the Biology department at the Secondly, as angiogenesis is a hallmark of tumor growth, we investigated Hebron University and worked as a lecturer teaching different courses in whether α-GalCer-stimulated iNKTs can be used to fight MM by reducing Biology. She is also a member of the Medical Technology Association in angiogenesis. We found that α-GalCer treatment significantly decreased West Bank. In 2009, she obtained a 6 month scholarship from Erasmus both tumor burden and microvessel density in the 5T33MM model. We Mundus Cooperation at the VUB in the VIB department of Structural also found that using conditioned media (CM) from α-GalCer-stimulated Biology/Redox Biology, where she participated in a publication as a co- proliferation, author. During this period she contacted Prof. Karin Vanderkerken to migration and network organization of endothelial cells (ECs) and search for a PhD position. In 2010, she got another scholarship from induced apoptosis. We further investigated the mechanisms behind this Erasmus Mundus to start her PhD study in the department of Hematology antiangiogenic effect and found that CM+Gal can functionally trigger the and Immunology under the supervision of Prof. Karin Vanderkerken and JAK-STAT signaling pathway and activates several transcriptional factors Prof. Eline Menu. Her research was focused on identifying the role of a such as IRF-1. In conclusion, stimulation of iNKTs can potentially activate unique subset of T cells called invariant natural killer T cells in MM anti-tumor defences, therefore controlling the functionality of iNKTs could immunotherapy. Her scientific research has led to three publications in be a promising treatment scheme in MM patients in the future. international, peer-reviewed journals as a first author. After graduation, iNKTs (CM+Gal) reduced neovascularization, viability, she will return back home to re-join the academic work in the Hebron University but with a new experience and a wider view in relation to medical sciences.