‘All forms of childhood cancer are rare,’ says Dr. Karin Sanders, acting group leader of the Clevers group e.t. and coordinator of the new Central Máxima Organoid Biobank (CMOB). ‘For many of these tumors, there are only very limited models available to study them in the lab. The models that do exist – for example cell lines or mice – do not always correspond well with the original tumor in the child's body.’
Mini-tumors of childhood cancer
A more recent type of research model to simulate tumors in the lab is the organoid – 3D mini-organs. When grown from tumor tissue, they are called tumor organoids. 3D mini-bowels were the first organoid model developed. Since then, scientists, including research group leader dr. Jarno Drost, have also succeeded in making these models available for research into certain types of childhood tumors. For example, in collaboration with prof. dr. Marry van den Heuvel-Eibrink, he developed the first organoids of Wilms tumor, a kidney tumor in children, and rhabdoid tumors in his group. Together with Frank Holstege's group, he also developed organoids from rhabdomyosarcomas.
‘Every tumor is different. This means that a different culture protocol is required for each tumor type in order to properly grow them in the lab into the 3D mini-tumors that we can use for research,’ says Drost. ‘It takes a lot of time and money to do this successfully, and researchers need very specific knowledge to develop organoids.’
Various research groups at the Máxima Center are already working with organoids, for example for research into targeted therapies and to gain insight into the effect of immunotherapy. They often grow them from tumor tissue from children who have been treated at the Máxima Center, provided parents or child have given their approval. With the CMOB, project leaders Karin Sanders and Jarno Drost aim to take the use of technology for childhood cancer research to a higher level.
Sanders: ‘We will include childhood tumors in this central biobank for organoids for which culturing protocols have already been developed by various research groups at the Máxima Center. We will start with nine different types of childhood cancer, including brain tumors, a bone tumor and a liver tumor. We will centralize the development, standardize every step in the process and make it traceable. We will implement strict quality controls and fully map the properties of the organoids. We will also develop clear step-by-step instructions on how to grow them. This ensures that not only we, but other researchers can also grow these models well.’
Wider research community
The project is financed by KiKa and by the National Growth Fund of the Dutch government, as part of Oncode Accelerator. This makes the organoids available to the broader research community. Drost leads the organoids innovation platform within Oncode Accelerator. He says: ‘As part of Oncode Accelerator, anyone carrying out research into childhood cancer can apply for the use of the organoids in our new Biobank. These are primarily fellow researchers at the Máxima Center, but in the long term external researchers and companies can apply too, for example to test new medicines for childhood cancer.’
In conversation with children and parents
Sanders and Drost are aware that the use of patient tissue for the Central Máxima Organoid Biobank involves ethical considerations. Sanders: ‘We think it is very important to discuss the use of patient tissue for this purpose with children and parents. For example, does it feel different when the tumor material is used to make organoids than when it is used for genetic research? We have appointed a postdoctoral researcher who will conduct specific research into this and, among other things, interview children with cancer and their parents. We want to inform the way we use the organoids from the biobank by what emerges from this ethical research.’
The ultimate goal of the research with the organoids is a better understanding and better treatment of childhood cancer, just like all research with tissue from children treated at the Máxima Center. Drost: ‘This project makes new fundamental research into childhood cancer possible: how does this tumor develop and grow, and can we find targets for new treatments? The special thing about the organoids that we include in this biobank is that not only we at the Máxima Center, but researchers from all over the world will soon be able to use them for research. We especially hope that this will accelerate the development of new therapies against childhood cancer.’