Immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-CTLA-4 blocking antibodies have transformed the treatment landscape for patients with advanced malignancies. Despite their clinical success, the ICIs are also associated with substantial risk of immune-related adverse events (irAEs) that cause can cause serious morbidity and mortality. Severe irAEs (grade = 3) occur in 15-55% of patients treated with antiPD-1/anti-PDL-1 and/or anti-CTLA4 antibodies. These severe irAEs require treated with immunosuppressants, but data suggesting that this compromises ICI efficacy are emerging Therefore, one of the main challenges in ICI therapy is to maximize benefit, while minimizing toxicity for patients. Currently the mechanisms of irAEs are not precisely understood and important questions that remain include the relationship between irAE characteristics such as site, severity, onset, management, and ICI efficacy. In addition, clinical biomarkers that can predict tumor responses and irAEs are lacking. Given that most irAE are mild and reversible if detected early and managed properly, biomarkers to predict irAEs are essential. In the UMC Utrecht we have set-up a prospective cohort of cancer patients (mostly melanoma and non-small-cell lung cancer) treated with ICI (single or combination), in which efficacy and toxicity are monitored and biomaterials (blood, feces, biopsies) are collected at different time-points. In this study we aim to:
1. Decipher mechanism of irAE following ICI therapy
2. Develop tools to predict irAE and ICI efficacy following ICI therapy
3. Determine the mechanistic link between irAE treatment and ICI clinical efficacy
To address our research questions we will make use of advanced immunological techniques including flow cytometry, tissue mass cytometry, single cell RNA and TCR-seq, tissue cultures, biomarker platforms luminex, Olink as well as in vitro functional assays, and 16S and Shotgun Metagenomic sequencing for microbiome analysis.
The CTI concentrates top expertise on immunology in one laboratory and conducts all research on immunological diseases of the UMC Utrecht. The CTI vision is to harness the immune system to cure infection, inflammatory disease and cancer. We do this by (1) working in multi-disciplinary teams of clinicians and researchers, (2) stimulating the flow from fundamental immunological insight to improvement of care, (3) closely linking education, research, diagnostics and care, and (4) training students and professionals to obtain a broad career perspective. Together the CTI provides an international, dynamic and stimulating work environment.
The UMC Cancer Center aims to continuously improve the outcome of patients with cancer. Innovative research is performed based on strong collaborations between basic, translational and clinical scientists.
The candidate is expected to:
have a background in immunology/cancer research, work well in a team, can
communicate data at scientific meetings and by publications in scientific journals. The candidate is
passionate about science.
The maximum salary for this position (100%) is € 4.481,00 gross per month based on full-time employment (work week 36 hours). This job is based on a temporary position for 4 years.
In addition, we offer an annual benefit of 8.3%, holiday allowance, travel expenses and career opportunities. The terms of employment are in accordance with the Cao University Medical Centers (UMC).
If you have any questions about this vacancy, please contact Mrs.Karijn Suijkerbuijk, Internist-Oncoloog, phone number: 06-55234706, e‑mail adress: K.Suijkerbuijk@umcutrecht.nl.
Acquisition based on this jobopening is not appreciated.