This project focuses on dissecting tumor-reactive T and NK cell responses after donor stem cell transplantation and exploration of adjuvant immunotherapeutic strategies to further boost anti-tumor immunity in these patients. Interested in Cancer Immunology and Immunotherapy and pursuing a PhD career? Join our exciting translational research group!

Every year, approximately 850 new patients are diagnosed with acute myeloid leukemia (AML). More than 50% of these patients have poor risk based on unfavorable mutations or cytogenetics or poor response to initial therapy. Allogeneic stem cell transplantation (alloSCT) is the only curative treatment option for poor-risk AML. Nevertheless, relapse rates are up to 40%.

Donor-derived NK and T cells play a crucial role in the curative graft-versus-tumor (GVT) response in AML patients after alloSCT. Robust alloreactive NK and T cell responses can be elicited, resulting in the establishment of clinical remission. Notably, a small pool of long-lived alloreactive memory T cells remains, which plays an important role in protective immune surveillance. Unfortunately, the beneficial GVT effect may be accompanied by graft-versus-host disease (GVHD). GVHD is the major cause of morbidity and non-relapse mortality after alloSCT. Therefore, various approaches to deplete alloreactive T cells, and thereby prevent GVHD, are applied in the clinic. The counter side of such strategies is increased risk of relapse. Hence, it is essential to minimize GVHD while preserving GVT immunity.

This warrants extensive longitudinal analyses of the recovery, phenotype and the functionality of the key immune effector cells after alloSCT in patients in relation to clinical outcome (relapse yes/no). Hereby, we aim to uncover the mechanisms that underly effective vs. dysfunctional graft-versus-tumor T and NK cell responses. These analyses include >35 parameter flow cytometry and advanced immunological assays. Together, the insights from these studies guide the subsequent development and exploration of strategies to further strengthen anti-tumor T and NK cell responses post alloSCT. These strategies include, dendritic cell (DC) vaccination, as DC are the key orchestrators of innate and adaptive immune responses, and adoptive transfer of NK cells. The last decade, we developed two unique and innovative ex vivo culture protocols to generate 1) high numbers of myeloid and plasmacytoid DCs and 2) highly potent NK cells from hematopoietic stem cells of the donor stem cell graft. Our DCs harbor exceptional NK and T cell stimulatory potential. In this project, we aim to further explore the optimal strategy and timing for post alloSCT DC vaccination and NK cell adoptive transfer in ex vivo and in vivo models.

For this project, we are looking for an ambitious PhD student. This four-year project should culminate in a PhD thesis. The PhD student 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 experiments. In addition, you are highly motivated to work in an interdisciplinary environment using state-of-the-art technologies and data-analyses tools. You have affinity with cell culture, (high-dimensional) flow cytometry, cellular immunology techniques and/or (bio-informatic/computational) data analyses. Animal experimentation is no objection to you.

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% vacation allowance, an 8.3% end-of-year bonus, and, depending on the position, an allowance of 47% to 72% for working irregular hours.
• Plenty of opportunities to develop yourself. For example, you can follow various courses via our online learning environment. A lot of attention will also be paid to your wellbeing and vitality. For instance, you can take advantage of:
  
  • a 40% discount on gym membership at the Radboud Sports Center.
  • the Company Support Team and a personal coach if you experience a life-changing event.
  • a financially favorable option to work less through a generation scheme if you are approaching state retirement age.
  • support with achieving a good work-life balance at every stage of your life. This includes advice and training (from ‘Millennial Dilemmas’ to ‘Your Career After 57’), activities at our own mindfulness center, and informal caregiving consultations if you have any questions about combining your work and caregiving tasks at home.
• 168 vacation hours per year based on a 36-hour working week. Want more vacation? You can buy additional vacation hours with your end-of-year bonus.
• 26 weeks of parental leave, of which 9 weeks are paid.
• Extra-favorable leave conditions. For example, our short-term caregiving leave is not 2 but 4 weeks per year and even 12 weeks per year for partner and child.
• Pension accrual with the ABP Pension Fund. Radboud university medical center pays 70% of the pension contribution.
• Discount on the supplementary packages of two collective health insurance policies and on ten other types of insurance, from home insurance to legal assistance.
• A travel allowance via our Employment Conditions Selection Model and 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. 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.