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Sebastiaan van Heesch: ‘We want to Identify faulty proteins to direct the immune system against cancer’

Like many talented young researchers, Sebastiaan van Heesch has traveled around to further develop his skills and knowledge. At the Princess Máxima Center he will now take a next step in order to increase  immunotherapy options for children with cancer. ‘My hope is that newer treatment options will help these children live more normal lives.’

Sebastiaan was born in Tilburg in 1985. In Utrecht he finished his Master's in cancer genomics and developmental biology cum laude. After a PhD at the Hubrecht Institute and a 5,5 year’s postdoc at the Max Delbrück Center for Molecular Medicine in Berlin, Germany, he moved back to Utrecht with his wife and two young kids. At the Máxima he is one of the principal investigators in the fields of immuno-oncology and systems biology. ‘In Berlin I optimized a technology called ribosome profiling, to study protein synthesis in human tissue biopsies. This technique lets us investigate the behavior of ribosomes – the protein factories of all cells – at a very high resolution. I witnessed ribosomes produce thousands of new, small proteins in human tissues such as the heart and liver. We now know that many of these microproteins have functions in diseases including cancer.’

Discover mistakes
The ribosome profiling technology will allow Sebastiaan to discover important mistakes some ribosomes make. This technology can be very valuable for childhood cancer, as it enables us to find and use such mistakes as therapeutic targets. This can be important for further innovation in immuno-oncology. Sebastiaan: ’Immunotherapy is not offered as a first line therapy for the treatment of pediatric cancer, even though it's been successful in adults. One reason is that immune systems of children are still developing, so it is difficult to predict how a child or specific tumor will respond to a therapy that was 'optimized' for adults.’

Find more targets
Another issue, Sebastiaan says, is that pediatric cancers generally have fewer genetic mutations, which makes them less suitable for immunotherapies directed against tumor specific DNA mutations. These mutations help the immune system decide which cells belong to the tumor (and need to be killed), and which cells are normal. ‘To overcome this, I will use ribosome profiling in order to find more targets for immunotherapy that are not visible as mutations in the tumor cell's DNA. The idea is that tumor cells express small parts of faulty proteins on their cell surfaces. Once we've identified these proteins, we will try to direct the patient's own immune system against all tumor cells that present these protein pieces.’

Normal lives

Sebastiaan’s work will not only be directed at tumors with poor prognosis, but also to provide alternative treatments with fewer side effects. ‘Long-term side effects are a serious issue. Immunotherapy is an attractive alternative to current treatment standards. Unfortunately, we are still at early phases on developing immunotherapy options for most pediatric cancers. My hope is that newer treatment options will help children live more normal lives, with fewer or no health consequences at later ages.’