For this four year project, we are looking for an ambitious postdoc with expertise and knowledge in cancer immunotherapy and genetic engineering of (immune) cells. Interested in Immunology and Immunotherapy for cancer? Join our exciting translational research group!

This project focuses on the development of a Good Manufacturing Practice (GMP) compliant platform to generate genetically engineered off-the-shelf allogeneic Natural killer (NK) cell therapy against Ovarian carcinoma (OC). OC is the most lethal gynecological malignancy and accounts for around 1,000 deaths in The Netherlands annually. Due to late diagnosis, most woman relapse after treatment, resulting in a 5-year survival of only 28-46%. As most woman with relapsed or metastatic cancer will die of progressive disease, there is a need for new therapeutic strategies. Adoptive allogeneic NK cell transfer can be an attractive treatment option for adjuvant immunotherapy.

Previously, we have developed a unique GMP-compliant culture system for the manufacturing of allogenic NK cell products from umbilical cord blood derived CD34+ progenitor cells. These products display high purity and a potent anti-OC reactivity in vitro and in vivo and are currently being investigated in a first in human trial. To improve scalability, accessibility and cost-effectiveness, this project focuses on greatly upscaling the NK culture process and cryopreserving them for on-demand application. To further improve the clinical efficacy in OC patient, we will engineer these cells with chimeric antigen receptors (CARs) and transpresented IL15/IL15Rα to improve tumor targeting and NK cell persistence.

You will work on optimizing the culture process for the generation of large numbers of NK cells in a new bioreactor system and translate this to a GMP compliant protocol. Furthermore, you will optimize the cryopreservation and work on the genetic engineering of these cells using lentiviral transduction. The effectiveness of the NK cells will be evaluated in vitro using our established methods, including flowcytometry based phenotyping, potency and killing assays, and in vivo using our established NOD/SCID/IL2Rgnull ovarian cancer xenograft mouse model.

The finalized culture, genetic engineering and cryopreservation process will be documented in an investigational medicinal product dossier (IMPD), which will be the basis for future phase I/IIa/IIb clinical trials using CAR-NK cells against OC.

Tasks and responsibilities

• Contribute to the development of new knowledge within the context of the department's research program.
• Design and perform scientific and immunomonitoring research.
• Write scientific publications and presents findings at scientific meetings.
• Work in a team with clinical and non-clinical PhD students, technicians and scientists.
• Discusse, plan and perform research in a stimulating environment.
• You are involved in NK cell culture in the GMP cleanroom facility.
• Write an investigational medicinal product dossier.
• Work in a highly international research group.

We are looking for a postdoc with enthousiasm and ambition to succeed in academic and translational research. It is important that you are highly motivated to work in an interdisciplinary environment at the cutting edge of science. Furthermore, you have well-developed social skills directed to working in a team, and excellent interpersonal and communicative skills.

In addition, you recognize yourself in the profile below:

• PhD degree in (Medical) Biology, Biomedical sciences, Molecular life sciences, or similar.
• Experience in cell culture, flow cytometry, cellular immunology techniques.
• Experience in molecular techniques including cloning, transfection and transduction.
• Art. 9 degree in animal studies is a prerequisite.

Fixed-term contract: 2 years with a possible extension.

Working at Radboud university medical center means that you are ahead of the curve and working together on the healthcare of the future. And there is more. Our secondary terms of employment are impressive. These are fully tailored to you thanks to our Employment Conditions Selection Model. At Radboud university medical center, you will be given trust, and you will take the responsibility to handle everything together. We provide annual courses, both professional and personal.

• In addition to your monthly salary and an annual vacation allowance of 8%, you will receive an end-of-year bonus of 8.3%.
• If you work irregular hours, you will receive an allowance.
• As a full-time employee (36 hours per week), you are entitled to approximately 168 vacation hours (over 23 days) per year.
• Radboud university medical center pays 70% of the pension premium. You pay the rest of the premium with your gross salary.
• You get a discount on health insurance as well: you can take advantage of two group health insurance plans. UMC Zorgverzekering and CZ collectief.

In addition to our terms of employment, we also offer employees various other attractive facilities, such as childcare and sports facilities. Want to learn more? Take a look at the CAO UMC.

Radboudumc

The research project 'Off-the-shelf stem cell-derived NK cells with chimeric antigen receptors and transpresented interleukin 15 to improve immunotherapy in ovarian cancer patients' will be conducted in the Translational Immunohematology 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 comprises five intermingled themes:

1. Development of novel strategies to boost antitumor immunity after allogeneic stem cell transplantation.
2. Co-signaling pathways involved in tumor immune escape.
3. DC-based vaccination strategies against hematological cancers.
4. NK cell-based immunotherapy against leukemia and ovarian cancer.
5. Early memory Chimeric antigen receptor T cell-based immunotherapy against B cell malignancies.

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 Departments of Gynecology, Medical Oncology and Hematology. We provide a stimulating work environment within a group of enthusiastic non-clinical and clinical researchers with a strong national and international research network and track record.

Radboudumc
Radboud university medical center is a university medical center for patient care, scientific research, and education in Nijmegen. Radboud university medical center strives to be at the forefront of shaping the healthcare of the future. We do this in a person-centered and innovative way, and in close collaboration with our network. We want to have a significant impact on healthcare. We want to improve with each passing day, continuously working towards better healthcare, research, and education. And gaining a better understanding of how diseases arise and how we can prevent, treat, and cure them, day in and day out. This way, every patient always receives the best healthcare, now and in the future. Because that is why we do what we do.

Read more about our strategy and what working at Radboud university medical center means. Our colleagues would be happy to tell you about it. #weareradboudumc