Research Assistant / Doctoral Candidate (PhD) (m/f/d)

Application deadline: 20/02/2026

The University Hospital of Würzburg is seeking to fill the following position as soon as possible as part of the
Collaborative Research Center/Transregios 205.

• A doctoral position in accordance with the German Academic Leave Act (WissZeitVG) (E13 TV-L, 65%), 3.5
  years
  
• An excellent scientific environment within the framework of an interdisciplinary DFG-funded transregional
  collaborative research center
  
• Structured supervision of the doctoral program within the Graduate School of Life Sciences at the University
  of Würzburg and extensive continuing education opportunities (http://www.graduateschools.uni-
  wuerzburg.de/life_sciences/)
  
• Close links to clinical and translational research and prospects for clinical translation
  
• The University Hospital of Würzburg promotes gender equality
  

• Independent scientific work within the scope of the research project described
• Planning, conducting, and evaluating cell biology, molecular biology, and (animal experimentation) studies
• Application of modern immunotherapy and gene editing technologies (including CAR-T, CRISPR/Cas9)
• Presentation of results at scientific conferences and publication in specialist journals

• Excellent university degree (master's/diploma/state examination) in biology, biochemistry, molecular medicine, or a related molecular subject
• Strong interest in tumor immunology, cell therapy, and translational cancer research
• Experience in molecular or cell biology methods is an advantage
• Highly motivated, able to work independently and as part of a team
• Very good written and spoken English skills (C1 level)

Project "Steroid hormones and cancer immunity – learning from adrenocortical carcinoma”

Project description

This project is interdisciplinary in nature and combines the expertise of the Department of Endocrinology and
Diabetology with that of the Department of Cellular Immunotherapy. It also benefits from a vibrant national
and international cooperation network.

Adrenocortical carcinoma is a rare and very aggressive form of cancer that responds poorly to existing
immuno-oncological therapies. Approximately 60% of patients experience an excess of glucocorticoids, which
inhibits the immune system and is associated with a poor prognosis. In previous work, we were able to show
that these tumors contain fewer immune-active cells and that important immune checkpoint molecules are
only weakly expressed, which explains the limited effectiveness of existing immunotherapies.

As part of the project, a novel cellular immunotherapy with genetically modified CAR-T cells was therefore
developed. ROR1 was identified as a suitable target antigen for adrenocortical carcinomas. ROR1-specific CAR-
T cells showed a strong antitumor effect in preclinical cell culture and animal models. However, this effect was
limited under conditions of glucocorticoid excess. Through targeted genetic modification of the glucocorticoid
receptor using CRISPR/Cas9, CAR-T cells were generated that are protected against this hormonal inhibition
and remain effective even under these conditions.

These results form the basis for an initial clinical study with ROR1-CAR-T cells (LION-1). The aim of the project,
which is now getting underway, is to further investigate the influence of various steroid hormones on CAR-T
cells and to analyze the safety and efficacy of the therapy in improved preclinical models in order to further
optimize its clinical application.

Specifically, the project encompasses

The project will investigate how sex hormones influence the function of CAR-T cells. Since a significant
proportion of patients with adrenocortical carcinoma have elevated androgen levels, there is a particular focus
on the influence of these hormones on the effectiveness of the therapy. The project will analyze how
genetically modified ROR1-specific CAR-T cells respond to different hormonal conditions.

In addition, new and improved CAR-T cell strategies are being developed and tested to overcome mechanisms
that can lead to an insufficient or diminishing response to therapy. The aim is to further increase the
effectiveness and sustainability of CAR-T cell therapy.

Another focus is the investigation of the mode of action of CAR-T cells in suitable, immunocompetent mouse
models of adrenocortical carcinoma. In addition, safety strategies are being evaluated that can be used to
control or reduce possible side effects of the therapy, for example, by specifically switching the CAR-T cells on
and off or by eliminating them in a controlled manner.

Overall, the project is making an important contribution to the development of personalized CAR-T cell
therapy for adrenocortical carcinoma and, beyond that, to the establishment of innovative cellular
immunotherapies for hormonally active tumor diseases.

• Anspruchsvolles, vielfältiges und entwicklungsfähiges Aufgabengebiet
• Attraktive Bezahlung nach TV-L inkl. Jahressonderzahlung
• Aus- und Weiterbildung in der eigenen Akademie
• Betriebliche Altersvorsorge
• Betriebskindertagesstätte mit verlängerten Öffnungszeiten
• Betriebssportangebote
• Flexible Arbeitszeiten dank Gleitzeitregelung
• Jobrad
• Mitarbeiter Angebote