Our primary interest aims at understanding the function of professional antigen presenting dendritic cells (DC) as major regulators of the immune response:
1) to gain better insight in the complex cell signaling and communication between DC and T cells,
2) to optimize immune responses against cancer.
I initiated my independent Tumour Immunology lab in 1985, with a primary interest in understanding the molecular mechanisms that regulate immune cell adhesion and migration of immune cells (Nature 1989, 1994), uptake of pathogens, such as HIV and Ebola, by DC and the capacity of different types of DC to present tumour antigens (Cell 2000).
Being keen to translate results to the clinic, the possibility to grow dendritic cells at the end of the previous century, offered us for the first time the opportunity to clinically exploit my knowledge on molecular mechanisms. At Radboud university medical centre (Radboudumc), we built a GMP facility to produce DC based cancer vaccines. We were amongst the first groups worldwide (Nature Medicine 2004, Clin Cancer Res. 2003, 2009, 2010), demonstrating how important route of administration of vaccines was for good clinical outcome (Nat. Biotechnology 2005) and how potent naturally circulating blood dendritic cells are in initiating immune responses in vivo (Clin. Cancer Res 2016, Cell Rep. 2017). New developments in the group are aimed at overcoming tailor made time-consuming and expensive generation of DC in vitro or isolation from the blood under GMP conditions for each patient. To this end we have developed a biodegradable nanoparticle platform to facilitate direct targeting of DC in vivo, exploiting DC subset specific antibodies coated on PLGA based nanoparticles that contain antigen and DC activating adjuvants. Current efforts are aimed at translating this PLGA based nano-medicine platform towards the clinic. A further extension of this work is the development of entirely ‘synthetic DC’ to directly activate T cells for use in tumor immunology (Chemical. Science 2013, 2014, ACS Chem Biol. 2015, Nature Imm Reviews 2017). Within the framework of the Oncode Institute and the Institute for Chemical Immunology (ICI), we collaborate with chemistry groups to further invest in exploiting various types of scaffolds to manipulate immune the immune system. At the same time these scaffolds are used as a tool to increase our knowledge of DC-T cell communication and to better understand the tumor microenvironment.