Ghent University Hospital brings hope for patients with new facility and groundbreaking research

We bet you didn’t know that enthusiastic biohackers are hard at work right here in Ghent. What’s more, they’re putting our city on the map as the European hotspot for personalised healthtech.

You’ll have to forgive us for a moment, but for this article, we’re dusting off the alphabet soup and letting the acronyms fly. However, those who can look past the jargon will see that Ghent is a true pioneer in cell and gene therapy. Plus, we added a glossary.

With the construction of an advanced production facility and the launch of the European ATTRACT study, Ghent University Hospital is clearly leading the way in personalised care. We spoke with Prof. Bart Vandekerckhove, Prof. Barbara De Moerloose, Dr Joline Ingels, and Dr Tim Desmet about how pioneering research into cell therapy creates not only economic value but, most importantly, increases the survival chances of (young) cancer patients. ‘I truly feel that we’re working on something important,’ says Bart.

From the early days to Good Manufacturing Practice

Prof. Bart Vandekerckhove is no newcomer to the field of cell and gene therapy. From day one as a physician, he was driven to develop treatments based on living cells. Together with the Belgian Red Cross-Flanders, he co-founded the cord blood bank and helped establish the Good Manufacturing Practice (GMP) unit at Ghent University Hospital.

That unit — think of it as a high-tech laboratory within the hospital — received its first official accreditation in 2016. ‘We started here with a very small project,’ Bart recalls. ‘Our initial focus was on a specific cell therapy for patients who developed virus-related complications after a stem cell transplant, such as CMV.’

A decade later, that niche solution has grown into a broad platform. ‘For instance, we have a close collaboration with the Faculty of Pharmaceutical Sciences, where together we developed lipid nanoparticles (LNPs) to target cancer cells in patients. Around 15 people now work in our cell and gene unit. Next year, Dr Joline Ingels will take the helm, as I’m retiring.’

An LNP revolution

Dr Joline Ingels saw the number of projects grow exponentially. ‘That’s partly thanks to the production process we developed to make lipid nanoparticles,’ says Joline, ‘the tiny lipid “bubbles” that carry the RNA. Early cancer vaccines were primarily cellular therapies using each patient’s own cells. That made manufacturing these vaccines particularly complex: you have to harvest those cells from patients, which isn’t always straightforward. Additionally, initial quality varies significantly. One patient can be sicker than another. But the treatment can be delivered far more straightforwardly using lipid nanoparticles, which is why we launched that collaboration. Then came the COVID-19 pandemic, and successful vaccine makers such as Pfizer and Moderna started deploying this technology at scale. That certainly accelerated things.’

‘These days, I’m responsible for the day-to-day running of the projects and the team,’ Joline adds. ‘We’re particularly delighted that funding for the newer, larger GMP unit has been secured and that we can start building.’

High demand

Naturally, there are more projects because the demand from different research groups has increased. ‘From the formulation of a therapy, right through to development and administration, we can do it all in‑house here,’ Bart explains. ‘For example, we currently have a project with VIB. They’ve developed a new treatment approach and want to test it in patients. That’s why we jointly submitted a project proposal to secure funding. That’s how we usually proceed.’

‘Partners come to us because we’re the only Belgian institution producing lipid nanoparticles,’ says Tim Desmet. ‘That’s why we’re keen to engage with other research centres. If they need lipid nanoparticles, we’re happy to produce them.’

‘What’s more, hospitals are increasingly looking to produce CAR‑T cells on site,’ Bart adds. ‘Which, in a way, is logical. Now, the logistics are fairly complex. The patient’s blood is drawn at the hospital. It then goes to a pharmaceutical partner, where the CAR‑T product is manufactured. Quality control must be carried out. Finally, the product must be transported back to the hospital for administration to the patient. Those are a lot of extra steps that are essentially unnecessary and time-consuming.’

The aim of the new unit: building bridges to the industry

The investment in this new GMP unit is driven by several concrete objectives. ‘First, in the new facility we can make a greater contribution to academic developments,’ says Tim. ‘It’s still our primary goal to research new therapies. Some of them may then progress into industry, if it’s relevant. For instance, Novartis’s CAR‑T therapy (the standard procedure here) was first developed at the University of Pennsylvania. So we certainly don’t aim to compete with commercial companies. Think of it rather as enabling research that can feed into industry.’

‘Second, we want to provide a service offering for companies. We can produce treatment formulations for them or collaborate on clinical studies so they can obtain specific accreditations.’

‘Depending on the type of research, we also work with researchers to assess market potential. If there is market potential, we gather sufficient data to support it and assess whether we can create a separate spin-out. We also receive support from the Technology Transfer service for that.’

'Finally, some of our researchers move on to Ghent-based companies, which is healthy. Others start in a company and later join us. Ultimately, it depends on what you want for your career.’

The new GMP unit

The new unit is scheduled for completion in autumn 2027. It will be housed in the Nobel I Tower and take up an entire floor, which is around 1,000 m². About half of that will be fitted out as cleanrooms.

‘With cleanrooms, you move from an uncontrolled space into a controlled one,’ Bart explains. ‘There are different grades: D, then C, then B. Each step is about ten times cleaner. Eventually, you work in Grade B with your hands inside a Grade A cabinet. That last level is completely particle-free.’

‘You enter through a Grade D area, then you can go either into Grade C and B production rooms for starting materials, or into Grade C and B production rooms for cell and gene therapy. In the starting‑materials rooms, we work with bacteria and viruses. Given the high risk of contamination, we want to keep it as far away as possible from cell and gene therapy production. Additionally, each room has its own ventilation system to prevent cross-contamination. That’s the only way to work safely. We’ll also have isolators there so we can prepare individual doses.’

‘This cleanroom already includes rooms for when the hospital starts routinely preparing CAR‑T treatments for our own patients. We could run up to six productions at the same time. In addition, we have three more rooms for manipulations, such as cell maturation and cell culture. Naturally, all of that has to happen at the cleanest end of the unit.’

International importance

‘It’s thanks to the GMP unit that we can play at an international level,’ Bart says. ‘We’re talking to people in Norway, Paris, the Netherlands, Italy, and more. With this facility, we can set up all kinds of projects with (foreign) institutions and more easily seek funding. It also clears the way for other projects.’

‘The fact is that Europe’s regulatory framework is pretty strict,’ Tim explains. ‘If you don’t have facilities that meet specific requirements, you’re simply not allowed to do the kind of research we’re doing here. But if you can’t take part in research projects, you can’t attract extra funding. And without that, you can’t push academic developments forward, so they won’t feed through to industry in the long run either. It’s a real domino effect.’

‘So if you’re asking about the impact of this new unit, it’s clearly huge. Not just for patients, the hospital, and the wider healthcare system, but also for training and for the economy.’

CAR‑T

The results from various CAR-T studies are often remarkable. Patients who have run out of options, who no longer respond to the standard mix of transplant and chemotherapy, can still go into remission after a CAR‑T treatment. ‘The next step is to see whether we can make them just as successful for solid tumours,’ Bart says. ‘We’re now developing a CAR‑T for kidney cancer. We’ll treat around ten patients and assess whether the therapy delivers the desired results. If it doesn’t, we’ll keep refining it. There’s a wealth of expertise at Ghent University, which will undoubtedly help.’

‘It’s also worth noting that this immunotherapy may be applicable to other types of disease,’ Tim adds. ‘At the end of last year, we treated the first MS patient in Belgium with CAR‑T cells, as part of a clinical study involving Prof. Guy Laureys and Prof. Tessa Kerre. So CAR‑T isn’t just for cancer, it’s increasingly being used for autoimmune conditions too.’

Closing the gap with an international study (part of the ATTRACT call)

To give an example of CAR‑T in practice, let’s zoom back in on today, more specifically the paediatrics department at Ghent University Hospital. The paediatric haemato-oncology department, led by Prof. Barbara De Moerloose, is highly regarded in Belgium and beyond. For conditions such as acute lymphoblastic leukaemia (ALL), it is the national reference centre. They know better than anyone that some patient groups need better options.

‘We’ve been using commercial CAR‑T products, such as those from Novartis, since 2015,’ Barbara says. ‘In early 2016, we even treated the first patient in Europe. These medicines do come with strict government reimbursement criteria, though. A patient must have relapsed for a second time, have a condition that no longer responds to chemotherapy, or have relapsed after a stem cell transplant before they’re eligible. That’s obviously a problem for patients who don’t meet those criteria.’

The numbers are small - the team has seen around 50 patients over the past ten years - but every child counts. That’s why Ghent University Hospital is joining the international ARI‑chALL study, part of the ATTRACT call. In Belgium, Kom op tegen Kanker is co-funding the effort, representing an investment of more than €1.3 million.

‘It’s an international collaboration with Spain, France and the Netherlands,’ Barbara explains. ‘Phase 1 is pure tech transfer. Over the first 18 months, we have to prove that we can develop exactly the same high-quality product here in Ghent as our Spanish colleagues. Because it’s a medicine, the quality requirements are extremely strict. For the Federal Agency for Medicines and Health Products (FAMHP), everything has to be documented in detail. Only once that validation is complete can we start the clinical phase for Belgian patients.’

A living medicine that stands guard

In the second phase, which will run for five years, the team aims to treat approximately 70 patients across all participating countries, including 5 in Ghent. That may sound modest, but the impact on those children is immense.

‘The standard approach after an early relapse is chemotherapy followed by a stem cell transplant,’ Barbara explains. ‘It’s a gruelling ordeal for the body, with many potential side effects and longer-term risks, such as infertility or secondary tumours. Those patients essentially require lifelong follow-up. CAR‑T therapy is fundamentally different. Immediately after treatment, there can be side effects - like a strong reaction similar to a severe flu, with fever and chills - but that’s temporary.’

The big advantage is the therapy’s “intelligence”. ‘The product remains in the body for life,’ Barbara says. ‘These are vigilant cells that will immediately attack if a dormant leukaemia cell ever wakes up.’

The ambition goes beyond this single study. The ultimate goal is to secure formal approval via the European Medicines Agency (EMA) for academic manufacturing. ‘If we can produce this therapy in-house as standard care, we democratise access,’ Barbara explains. ‘That would give other patients a chance at this treatment too, high-risk patients at first relapse, for example.

‘It’s cheaper, faster and, above all, more accessible for people who currently have no options left. And that would only be the beginning of something much bigger. I genuinely think we’re only at the start of a full rollout of multiple CAR‑T therapies. We have a major opportunity on our hands, and a very promising future.’

Pictures: © Ghent University Hospital