prof. Karim Vermaelen (MD, PhD)
Associate professor, Faculty of Medicine and Health Sciences, UGent
Principal investigator, Tumor Immunology Laboratory of the Dept. of Pulmonary Medicine
Co-founder of the ION (Immuno-Oncology Network) Ghent
Board-certified pulmonary physician and thoracic oncologist
Our preclinical research investigates the interactions between lung cancer and the immune system, with a special focus on dendritic cells (DCs). DCs can function as sentinels and alert T-lymphocytes (the soldiers of our immune system) about the presence of danger in our body, including developing tumors.
We have previously uncovered a novel way by which lung tumors corrupts the function of DCs in order to escape immune control. This involves reprogramming of the DC’s micro-RNA repertoire. Micro-RNAs are small non-protein coding RNAs that can “veto” the translation of genes into proteins wihin a cell. Intriguingly, the micro-RNA signature of these “corrupt” DCs predicts a worse outcome in lung cancer patients.
We are now exploring the therapeutic potential of immunostimulatory DCs generated in vitro from patient blood. By loading these cells with mRNA prepared from the patient’s own tumor, a cellular vaccine is thus obtained. Following years of pre-clinical development, and through close collaboration with the GMP Production Unit of Ghent University Hospital (prof. B. Vandekerckhove), we now have 2 DC vaccine prototypes approved by regulatory authorities for testing on human subjects. Two clinical trials in lung cancer patients are active for recruitment.
In addition, we are building a unique prospective collection of blood samples from immune checkpoint-treated lung cancer patients. Combining flow-cytometry and cutting edge transcriptomic analysis (collaboration with prof. K. De Preter), we will work to uncover patterns in the systemic immuno-reactome that are associated with objective tumor response c.q. resistance to these treatments. The aim is to develop of patient-friendly, minimally-invasive test for therapeutic prediction.
Through the thoracic oncology clinic we are also offering patients a wide portfolio of industry-sponsored clinical studies with the latest immunotherapy combination regimen in lung cancer.
- Vaccine Strategies to Improve Anti-cancer Cellular Immune Responses. Front Immunol, 2019
- An accelerated, clinical-grade protocol to generate high yields of type 1-polarizing messenger RNA-loaded dendritic cells for cancer vaccination. Cytotherapy, 2018.
- The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a micro-RNA signature with negative impact on clinical outcome. Oncoimmunology, 2016
- Lung tumours reprogram pulmonary dendritic cell immunogenicity at the microRNA level. International Journal of Cancer, 2014
- Non-coding RNAs and respiratory disease. Thorax, 2014
- Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. European Respiratory Journal, 2010
- Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nature Medicine, 2009
- State-of-the-Art Review: Pulmonary Dendritic Cells. Karim Vermaelen, Romain Pauwels, American Journal of Respiratory and Critical Care Medicine, 2005
- Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. The Journal of Experimental Medicine, 2001