Therapeutic vaccines, in combination with other therapies, are a promising form of immunotherapy for the treatment of cancer in children and adults. The vaccines 'train' the immune system to recognize cancer cells as foreign and then attack the tumor. The national partnership Oncode Accelerator, of which the Máxima is a member, therefore focuses on the development of new cancer vaccines, among other things.
Comparing billions of data points
The first step in developing a vaccine is to find the recognition point needed to train the immune system. This is a protein that sits on the outside of the cell and is also called an antigen. The production of this protein is controlled by the genetic code, the DNA and RNA, in the cell.
Simon Venneman, project manager in the Van Heesch group and involved in the research: 'DNA consists of 3 billion letters. By comparing DNA from tumor and normal cells, we hope to find landmarks. The difference between cells can be in just a few letters. With one of the two new devices, the Nanopore PromethION 24, we can map the genetic code very accurately. This is because, compared to common methods, it reads long strands of the code in a single pass. We can directly compare the billions of data points we find using specially developed computer programs based on artificial intelligence (AI). This is how we find the antigens that can serve as starting points for a vaccine.'
Validation
The researchers are using a second device to make sure that a DNA difference actually causes a protein on the cancer cell. 'With the Bruker TimsTOF Ultra, we are taking an important step. Whereas with the first device we try to find evidence of possible antigens, with this second device we can show that this antigen is actually produced in cells and is recognizable by the immune system. This is essential information to actually develop a cancer vaccine,' Venneman says.
Together with expert in this field Prof. Dr. Albert Heck of Utrecht University and also involved in the Oncode Accelerator partnership, this validation step is being carried out. An identical device has also been placed at Utrecht University to make optimal use of the knowledge of the Heck lab to generate detailed data. Also of the very smallest proteins. In addition, this allows twice as fast working and learning from everyone's experiences.
Flywheel
Having all the equipment in one place has many advantages explains Dr. Sebastiaan van Heesch, research group leader at the Máxima center, junior-investigator at Oncode Institute and vice-chair of the therapeutic vaccine working group of Oncode Accelerator: 'Thanks to the new facility, we don't have to send material and transfer research to a party outside the Máxima, which saves time. We will also see and learn for ourselves where we can further improve the analyses and the process. This way, we will significantly speed up the process of arriving at starting points for new vaccines.'
Next steps
Prof. Sjoerd van der Burg, professor of immunotherapy and solid tumors at Leiden UMC, Senior Oncode Institute investigator and chairman of the therapeutic vaccine working group of Oncode Accelerator: 'The opening of this facility is an important milestone. At the Máxima center, the first step is taken with the identification of specific antigens, after which we can determine within our working group which of these antigens are capable of eliciting a response from the immune system, in order to then design and test the most optimal vaccine possible in patients. It is very nice that the chain has now been set in motion to arrive at new vaccines for the treatment of cancer in children and adults.'
About Oncode Accelerator
Oncode Accelerator is a unique national collaboration coordinated by six partners: Leiden University, Leiden University Medical Center, Netherlands Cancer Institute, Princess Máxima Center for pediatric oncology, University Medical Center Utrecht and Oncode Accelerator Foundation. Oncode Accelerator improves and accelerates the development of new cancer therapies by involving patients earlier in the process. The program is a joint effort of more than 30 public and private partners from the 'oncology ecosystem'. Oncode Accelerator is co-funded by the National Growth Fund and collaborates with the Ministry of Economic Affairs and the Ministry of Health, Welfare and Sport.