Focus of research
I am the leader of the theme ‘Tumor Immunology’ of the Cancer Center Amsterdam, a new research institute that combines the research programs of the 2 University Medical Centers in Amsterdam. After my PhD I set up a research group that performs both pre-clinical and translational studies with focus on (immune)biology and treatment of B-cell malignancies with CLL as main disease serving as a B-cell malignancy model. These studies were combined with both phase 1, 2 and 3 clinical trials for which he started an international network. These efforts have positioned the research group as the foremost clinical and translational CLL Center in the Netherlands and enabled me to build a large countrywide CLL biobank. As exemplified by a recent invited editorial in one of the leading medical journals in this field I am positioned as renowned international expert in this field (see ref. 2). See below a listed selection of achievements:
- Basic/translational research:
- Tumor microenvironment (TME): In vitro models simulating the tumor microenvironment of lymphnodes have been created within my group. This enabled pivotal studies which uncovered the important role of the TME in this disease which contributed to the development of novel targeted inhibitors. In vivo confirmation of this findings were established in an adapted CLL mouse model.
- Functional genetic studies: I have set up an European network to study the relevance of specific recurrent genetic aberrations in CLL, especially in relation to drug sensitivity. This work contributed to recognition of specific mutations such as TP53 that are now routinely tested to guide treatment decisions
- Adaptive immune responses: I have developed a track record of studies on the adaptive immune system in CLL. As T cells are a very small minority of total leukocytes in CLL (<5 to 1%), sophisticated methods have been set-up to facilitate such studies. These efforts made our group one of the main contributors to current knowledge on T cell dysfunction in CLL.
- Clinical research: When I took over the chairman position of the Dutch/Belgian HOVON CLL working group end of 2014, there were no open or planned trials. I reorganized the group, established an alliance with the Nordic CLL study group and (re)strengthened ties with other European study groups (especially the German CLL study group) and with pharma-industry. This has resulted in multiple international multicenter trials with novel agents in which my institute serves as central diagnostic and research laboratory for Netherlands and Belgium. Greatest achievement in this field has been the Hovon-associated global phase 3 MURANO study of which I am the principal investigator, which resulted in the establishment of a (practicing changing) new standard-of-care treatment for relapsed CLL patients.