Severe Combined Immunodeficiency (SCID) disease affects 1 in 35,000 newborns annually, of which approximately 145 are babies in the European Union. These children are born without a functional immune system, making them seriously ill from infections. Without treatment, they often die within their first year of life. SCID is treated with blood stem cell transplantation. But what if there is no suitable donor?

Frank Staal is a molecular stem cell biology professor at Leiden University Medical Center (LUMC) and has developed a stem cell gene therapy to cure children with a specific form of SCID (RAG1-SCID). This was already successful in 2022 with a three-month-old boy. “His immune system is indistinguishable from a normal immune system,” says Frank Staal. In this article, you can read about the challenges and what it took to achieve this success.

Baby cured of SCID with stem cell gene therapy

“When we saw that we cured the child, we were euphoric,” says Frank Staal. “We also celebrated with a glass of champagne because of the remote corona”.

The LUMC is one of the two centers in the Netherlands where stem cell transplants for children occur. “Gene therapy is a very nice extension of that,” says Frank Staal. “If there is no suitable donor, we can apply stem cell gene therapy. We modify the body’s cells using viral vectors and return these cells. This has several advantages: for example, there is no risk of graft-versus-host disease.”

A phase 1 trial is currently underway. Frank Staal hopes to complete the first phase of the clinical trial within two years. “We have received many candidates but are very strict in the selection procedure. As a result, we see many children who do not officially have SCID or already have a suitable donor. We are now in talks with other countries to be able to cure patients there.”

Challenges with the vector

“Modified stem cells are returned to the body. This modification takes place using viral vectors. It took a lot of time in the lab to figure out how to make a vector that no longer replicates but can still integrate into the host’s DNA,” says Frank Staal. “Then you look for a party that can produce the vector on a large scale for all the quality tests and, ultimately, the clinical trials. Fortunately, we have Batavia Biosciences, a contract development and manufacturing organization (CMDO), just around the corner. They had no experience with this type of viral vector yet, but they did have experience with viral vaccines. In addition, they have a good reputation. Ultimately, they delivered a product that works excellently and has been used to cure the first patient.”

The collaboration with Batavia Biosciences

“I think our collaboration is unique,” says Frank Staal. “Traditionally, you give the vector to a production company, and after that, there is hardly any contact. Instead, Batavia Biosciences and the LUMC did it together.”

Wilfried Bakker, director of Science and Innovation at Batavia Biosciences, agrees. “Batavia Biosciences already had a lot of experience and expertise in the field of viral vaccines. Frank Staal’s project suited us well because viral vectors are similar to viral vaccines. We enter into a conversation and keep talking during the development process. That is what distinguishes Batavia Biosciences. In this way, we ensure that the quality of the product is maintained while the costs remain low. We do this, among other things, by creating a scalable process in which the product continues to meet the quality requirements. With our platform technology, we can also achieve this relatively quickly.”

“The recovery of the first patient is, of course, a huge milestone. I was overjoyed, and the team was super enthusiastic”, Wilfried Bakker continues. “Contributing to these kinds of projects is the biggest motivation at Batavia Biosciences.”

Next steps

Batavia Biosciences is building a new facility, which should be ready in 2024. “Our vision is to continue to grow in viral vaccines and virotherapy. For stem cell gene therapy for immune diseases and oncolytic therapy,” says Wilfried Bakker proudly. “In the new facility, we can use certain technology, which allows us to keep processes efficient. This advantage will keep costs low and viral vaccines and virotherapy will be more widely available.”

That is also important for Frank Staal. “Ultimately, you want to make it easier and more affordable for families to have their child cured of SCID and other immune diseases. We need enough viral vectors for this, not just at the current clinical trial level. Batavia plays a major role in this process because they developed the viral vector with us and are experts in scaling up these types of processes.”

Finally, Frank Staal says: “I think the outlook for gene therapy is favorable: one treatment is enough to cure a child for life. That is very special.”