Phd Candidate for The Division of Personalized Immunotherapies

**Reference number**:2025-0252** - Mainz - Full-time - HI-TRON Mainz - Personalized Immunotherapies **_“Research for a life without cancer" is our mission at the German Cancer Research Center. We investigate how cancer develops, identify cancer risk factors and look for new cancer prevention strategies. We develop new methods with which tumors can be diagnosed more precisely and cancer patients can be treated more successfully. Every contribution counts - whether in research, administration or infrastructure. This is what makes our daily work so meaningful and exciting._** The **Helmholtz Institute HI-TRON** is a collaboration of the German Cancer Research Center (DKFZ) with the Research Institute for Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz (TRON gGmbH), the University Medical Center Mainz and the Johannes Gutenberg University Mainz. The goal of the partnership is to develop effective immunotherapies and to identify novel biomarkers for assessing the effectiveness of treatment. To strengthen the HI-TRON team in Mainz, we are seeking a motivated and talented **YOUR TASKS**: Antibody-Drug Conjugates (ADCs) are a rapidly advancing class of cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic agents. Upon internalization into tumor cells, ADCs release their cytotoxic payload, causing targeted cancer cell death via DNA or microtubule disruption. Beyond their direct cytotoxic effects, emerging evidence shows that ADCs can also trigger immune activation. They may induce immunogenic cell death, activate the cGAS-STING pathway, promote dendritic cell maturation, and facilitate T-cell priming and tumor infiltration. Additionally, through their Fc domains, ADCs can engage natural killer (NK) cells to mediate antibody-dependent cellular cytotoxicity (ADCC), collectively reshaping the tumor microenvironment (TME). Understanding these immune-modulating effects is essential to optimize ADC-based therapies. In our study, we plan to systematically investigate two clinically relevant HER2-targeting ADCs, each bearing distinct cytotoxic payloads (Trastuzumab Deruxtecan and Trastuzumab Emtansine). These models will allow us to explore how payload differences influence both tumor cell killing and immune modulation within the TME. In addition, we will evaluate these ADCs in “cold” versus “hot” tumor settings. This will help us elucidate why ADCs may be more effective in immune-infiltrated tumors and identify the key immune players responsible for this effect. Furthermore, we aim to identify novel combination partners that could synergize with ADCs to enhance tumor control. This includes testing combination strategies such as siRNA-mediated inhibition of DNA repair using lipid nanoparticles (LNPs), co-administered with ADCs to enhance tumor cell vulnerability and immune response. Key Responsibilities: - Design and conduct experiments to evaluate the immune-modulatory effects of HER2-targeting ADCs - Analyze and interpret data related to anti-tumor immunity, cell death mechanisms, and DNA damage response - Present research findings, progress updates, and strategic input to the team - Collaborate effectively with a multidisciplinary team of scientists and technicians **YOUR PROFILE**: - Master’s degree in molecular biology, genetics, biochemistry, pharmaceutical sciences, bioengineering, or a related field - Strong interest in tumor immunology and drug development - Experience in cell culture, immunological methods, and/or preclinical animal models - Highly organized, quality-conscious, and able to work independently - Strong written and verbal communication skills in English - Collaborative mindset and effective interpersonal skills - Ability to meet deadlines with attention to detail and efficiency **WE OFFER**: **Excellent framework conditions: state-of-the-art equipment and opportunities for international networking at the highest level** **Access to international research networks** **Doctoral salary with the usual social benefits** **30 days of vacation per year** **Flexible working hours** **Possibility of part-time work** **Family-friendly working environment** **Sustainable travel to work: subsidized Germany job ticket** **Unleash your full potential: targeted training and mentoring through the DKFZ International PhD Program and DKFZ Career Service** **Our Corporate Health Management Program offers a holistic approach to your well-being** **ARE YOU INTERESTED?**: Then become part of the DKFZ and join us in contributing to a life without cancer **Contact**: Dr. Ibrahim Murathan Sektioglu Phone: +49 (0)6131/179816 **Duration**: The position is initially limited to 3 years. **Application Deadline**:30.09.2025