Interested in Immunology and Immunotherapy, join our team and exciting translational research program!

This project focuses on the preclinical exploration of novel immunotherapies against Acute Myeloid Leukemia (AML). Every year, approximately 500 new patients are diagnosed with AML. In 30% of these patients the prognosis is poor due to unfavorable characteristics of the leukemia cells. Allogeneic stem cell transplantation (alloSCT) can be a curative treatment for AML patients. However, relapse post-alloSCT remains a major problem. This emphasizes the need for more effective treatment options to maximally reduce tumor load prior to alloSCT and improve the window of opportunity for graft-versus-leukemia immunity.

To achieve these goals, hypomethylating agents (HMA), such as azacitidine and decitabine, are highly attractive because these agents are well-tolerated and exert direct anti-proliferative and pro-apoptotic effects on tumor cells. Interestingly, HMA can also modulate tumor immunogenicity and enhance T cell and natural killer (NK) cell responses, thereby promoting anti-tumor immunity. Recently in an explorative study, we observed improved relapse-free survival and enhanced frequencies of tumor-reactive T cells in patients treated with decitabine prior to alloSCT. Yet, still many poor-risk AML patients relapsed.

To prevent disease relapse and eventually cure patients it is important to provide extra boost of the tumor-reactive immune responses. Because of decitabine's immune promoting effects, combination treatment with cellular immunotherapy is a unique strategy with strong potential to establish long-lasting tumor control, without causing severe toxicity. In this regard, vaccination with natural dendritic cell (DC) subsets holds great potential, as DC are the key orchestrators of anti-tumor immunity.

Recently, we developed an innovative ex vivo culture protocol to generate high numbers of myeloid and plasmacytoid DC from hematopoietic stem and progenitor cells (HSPC), with exceptional T and NK cell stimulatory potential. This project aims at investigating the effects of decitabine exposure on tumor immunogenicity, as well as on priming of tumor-reactive T and NK cell responses in AML patients. Furthermore, HSPC-derived myeloid and plasmacytoid DC vaccines will be further developed as adjuvant immunotherapy for boosting of decitabine-primed tumor-reactive T and NK cell responses. We anticipate that these studies will provide rationale for combined immunomodulation by decitabine and DC-based immunotherapy to boost graft-versus-leukemia immunity, and establish long-lasting disease control.

For this project we are looking for an enthusiastic research technician, who in close collaboration with PhD students will perform independent experiments, document and report research results and contribute to scientific publications.

Tasks and responsibilities

• The technician contributes to the development of new knowledge within the context of the department's research program.
• Isolation and cryopreservation of mononuclear cells from patient' blood and/or bone marrow.
• Isolation of T and NK cells from blood and bone marrow for functional assays.
• Culture of myeloid and plasmacytoid dendritic cells for functional assays.
• Independent performance of cellular immunological assays and multi-color flow cytometry assays.
• Presentation and discussion of research data (written reports, team meetings).
• Translation of research findings to methods and protocols.

• Degree of Laboratoria technician (hlo level).
• You can work independently, are pro-active, enthusiastic and a team-player.
• You have affinity with cellular immunological assays.
• You have ample experience with cell culture, multi-color flow cytometry and cellular immunology techniques.

Fixed-term contract: 1 year with a possible extension.

Upon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG) and there will be, depending on the type of job, a screening based on the provided cv. Radboud university medical center's HR Department will apply for this certificate on your behalf.

Read more about the Radboudumc employment conditions and what our International Office can do for you when moving to the Netherlands.

Radboudumc

The research project will be conducted in the Immunotherapy research group of the Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands. We focus on the characterization and modulation of immune reactions involved in the antitumor response against cancer. Our translational research program encompasses four intermingled themes:

• Development of novel strategies to boost antitumor immunity after allogeneic stem cell transplantation. Co-signaling pathways involved in tumor immune escape.
• DC-based vaccination strategies against hematological cancers.
• T- and NK cell-based immunotherapy against leukemia, multiple myeloma and ovarian cancer.

Our research is embedded in the Radboud Institute for Molecular Life Sciences (RIMLS). The studies indicated in this vacancy will be performed in close collaboration with clinicians of the Department of Hematology at the Radboudumc. We provide a stimulating work environment within a group of enthusiastic non-clinical and clinical researchers and technicians with a strong national and international research network and track record.

Radboudumc
Radboudumc strives to be a leading developer of sustainable, innovative and affordable healthcare to improve the health and wellbeing of people and society in the Netherlands and beyond. This is the core of our mission: To have a significant impact on healthcare. To get a better picture of what this entails, check out our strategy.

Read more about what it means to work at Radboudumc and how you can do your part.