This KiKa-funded project focuses on establishing a novel cellular immune therapy for acute myeloid leukemia (AML). Interested in Cancer Immunology and Immunotherapy and pursuing a PhD career? Join our exciting translational research group!

Currently, for both childhood and adult AML the 5-year overall survival is poor, and patients do not survive due treatment-related toxicity or relapse. Therefore, potent adjuvant therapies are needed to improve outcome with limited treatment-related side effects.

Adjuvant allogeneic natural killer (NK)-based immunotherapy is a promising and well-tolerated therapeutic approach for AML, exerting encouraging anti-leukemic activity. However, further enhancement of its therapeutic efficacy is needed to achieve more and longer-lasting clinical responses. We therefore established a GMP-compliant culture system to manufacture off-the-shelf allogeneic Natural Killer (NK) cell products from umbilical cord blood (UCB)-derived CD34+ hematopoietic progenitor cells (HPC). In non-clinical studies this HPC-NK cell product (devoid of allogeneic T cell-contamination) exerts potent anti-AML reactivity.

Our clinical studies showed that nonengineered HPC-NK cells can be safely administered to AML patients with transient anti-leukemia reactivity. To further increase clinical efficacy, we propose to engineer HPC-NK cells with multiple chimeric antigen receptors (CARs) to maximize AML-directed cytotoxicity, combined with transpresentation of IL15 tethered with IL15Rα (tIL15) to improve CAR-NK cell expansion and activity. The aim of this project is to establish an off-the-shelf CAR-HPC-NK cell product combined with tIL15, for immunotherapy of (childhood) AML patients with refractory disease. For this, we will apply viral transduction with (single or multi-antigenic) CARs, combined with tIL15 in our GMP-compliant HPC-NK production protocol. Furthermore, we will evaluate anti-AML effects and off-tumor toxicity in vitro and in preclinical mouse models.

This project aims to deliver a potent off-the-shelf CAR-tIL15 HPC-NK cell product with improved expansion, anti-AML reactivity and limited on-target off-tumor toxicity as an effective on-demand adjuvant immunotherapy, to prolong relapse-free survival and potentially cure (childhood) AML patients.

For this project, we are looking for an ambitious PhD student. This four-year project should culminate in a PhD thesis. You will participate in the Radboudumc Graduate School and Radboud Research Program "Treatment Improvements for Severe Hematological Diseases".

Tasks and responsibilities

• Contribute to the acquisition of knowledge and new insights within the context of the department’s research program.
• Design and perform scientific research.
• Write scientific publications and present research data at scientific meetings and conferences.
• Work in a team with clinical and non-clinical PhD students and scientists.
• Discuss, plan and perform research in a stimulating environment.
• Work in an international research group.

Our ideal candidate has a Master degree in (Medical) Biology, Biomedical sciences, Molecular Mechanisms of Disease, Molecular life sciences, Medicine or similar. You have the enthusiasm and ambition to succeed in translational academic research. You are assertive, ambitious and a team-player. Further, you have well-developed social skills directed to work in a team, and excellent interpersonal and communicative skills.

You are able to independently plan and carry out highly complex immunological experiments. In addition, you are highly motivated to work in an interdisciplinary environment using state-of-the-art technologies. You have affinity with cell culture (of primary immune cells), molecular techniques (e.g. cloning and/or CRISPR), viral transduction, (high dimensional) flow cytometry, cellular immunology assays and data analyses. Animal experimentation is no objection to you and you have an Article 9 Certificate of the Experiments on Animals Act.

Fixed-term contract: 4 Years.

At Radboud university medical center, you build on your future. We are committed to providing the best care, education, and research. And we are true to our word, because we help you develop and seize opportunities and give you the room to grow. As an employer, we believe that employees should feel vital and happy at work in all stages of life. We are also committed to creating a healthy and safe working environment. Our employment conditions contribute to that. What we offer:

• Upon commencement of employment, you will start at scale 10A, step 0 (€ 3.017 based on a full-time appointment). Over a maximum period of 4 years, you will progress to scale 10A, step 3 (€3.824 based on a full-time appointment). You will also receive an 8% holiday allowance, an 8.3% end-of-year bonus, and a 47% to 72% bonus for working unsocial hours.
• 172 vacation hours per year based on a 36-hour working week. (As of 1 January 2025, you will receive 176 vacation hours.)
• An Employment Conditions Selection Model, allowing you to use part of your employment conditions to your choosing. For example, you can use your gross salary to purchase additional vacation hours or hours for providing informal caregiving. Or, for example, you can use your gross end-of-year bonus to purchase a bicycle, so you pay less tax.
• Plenty of opportunities for personal development. You can take a variety of courses in our online learning environment.
• Your well-being and vitality are a priority. For example:
  
  • Save time for work-life balance leave.
  • A 40% discount on a sports membership of the Radboud Sports Center.
  • Healthy Professionals program to help you manage your energy.
  • Company Support Team and a personal coach if you are going through a life-changing event.
  • Financially beneficial working less through a Generation Scheme as you approach state pension age.
• Support in achieving a good work-life balance at every stage of your life. Examples:
  
  • Advice and courses on, for example, 'Millennial dilemmas' and 'Your Career After 57'.
  • Activities at our own mindfulness center.
  • Informal caregiving consultations if you have questions about juggling work and caregiving responsibilities at home.
• In addition to statutory pregnancy and maternity leave, Radboud university medical center offers 26 weeks of parental leave, nine of which are paid. In addition, as a partner you can take a maximum of five weeks of supplementary partner leave. During supplementary partner leave and parental leave, we supplement the UWV benefit up to 100% of your salary.
• Pension accrual at the ABP Pension Fund. Radboud university medical center pays 70% of the pension premium.
• Discounts on supplementary packages of two group health insurances and ten other types of insurance, from home insurance to legal assistance.
• As of 1 October 2024: an allowance for your commuting costs of € 0.18 per km up to a maximum of 40 km one way. If you use public transport to commute, we will fully reimburse the public transport costs (2nd class). If you regularly work from home, you will receive a working from home allowance of € 2.35 per day.

Radboudumc

You will work in the Immunotherapy research group of the Laboratory of Hematology, Department of Laboratory Medicine, Radboudumc, Nijmegen, the Netherlands. We focus on the characterization and modulation of anti-tumor immune responses in cancer patients. Our translational research program encompasses four 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. T and NK cell-based immunotherapy against leukemia, multiple myeloma and ovarian cancer.

Our research is embedded in the Radboud Research Institute. The studies indicated in this vacancy will be performed in close collaboration with clinicians of the Department of Hematology at the Radboudumc and the Prinses Máxima Center. 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
Welcome to Radboud university medical center (Radboudumc), where scientific breakthroughs are born through the curiosity and passion of our collaborating researchers in a vibrant environment. We believe trust and excitement are crucial elements to achieving our goals, and we approach our research as teams and with the utmost rigor to make a significant impact on health and healthcare. Our researchers are driven by their fascination with the biological, psychological, and sociological mechanisms underlying health and healthcare. They collaborate with partners from all over the world to improve health outcomes for all. Radboudumc unites patient care, research, education, and corporate learning, which allows us to approach our mission to shape the health and healthcare of the future in an innovative and person-centered way.

Our ambition is to lead the way in the pursuit of prevention, sustainability, meaningful care. We believe that through our research, we can significantly improve the health and well-being of society. Join us on our mission to make a difference in healthcare. Become a part of our community of gifted researchers, professionals or patient partners who are dedicated to making a real impact on population health and healthcare.

Read what it is like to do a PhD at the Radboud University Medical Center.