BMC Seminar Thursday 7th of March at 12:00 in room 201 Læknagarður
Speaker: Dr. Sóley Þórðardóttir, Biomedical scientist at the Central Clinical Laboratory, Landspítali University Hospital.
Title: Hematopoietic stem cell-derived products for cancer immunotherapy.
Abstract: Over the past decades it has been demonstrated that the immune system has an indispensable role in tumor control. This has consequently driven the development of novel strategies that mediate tumor clearance by initiating new or boosting existing immune responses against the malignant cells. An example of one of the first successful immunotherapeutic strategies that has been developed is allogeneic stem cell transplantation (alloSCT). AlloSCT is a powerful cellular immunotherapy for patients with aggressive hematological malignancies, and to date, is the only possible curative option for many patients. The therapeutic effect is mediated by lymphocytes, mainly T cells and natural killer (NK) cells, originating from the donor graft that recognize the patient’s tumor cells as foreign and subsequently eradicate them; in brief called the graft-versus-tumor (GVT) effect. However, in a significant number of patients the induction or reactivation of these immune responses is inadequate, contributing to disease progression or relapse. This illustrates the urgency to develop novel interventions to initiate and/or boost more potent GVT immunity and prevent tumor relapse post-alloSCT.
In this talk I will present the results of my PhD project, which was performed at Radboud university medical center in Nijmegen, The Netherlands. In this project, we worked on the development of novel immunotherapeutic strategies to boost GVT immunity post-alloSCT. We developed protocols for ex vivo-generation of different dendritic cell (DC) subsets and NK cells from CD34+ hematopoietic stem and progenitor cells (HSPCs). During this process, we discovered that inhibition of the aryl hydrocarbon receptor (AhR), using the antagonist StemRegenin 1 (SR1), significantly promoted the differentiation of pDC, BDCA1+ mDC and BDCA3+ mDC subsets from CD34+ HSPCs ex vivo. Furthermore, SR1 was found to improve the differentiation and activity of HSPC-derived NK cells. These HSPC-derived cell products could be used for DC vaccination and adoptive NK cell transfer post-alloSCT, respectively. Potentially, these products could also be therapeutic options in non-transplant setting of hematological malignancies and for solid cancers.