Using a patient’s own immune cells to recognise and fight cancer is now a reality in Luxembourg, thanks to the use of CAR-T cells. For Sébastien Rinaldetti, a haemotologist, oncologist, and clinician-scientist at the Centre Hospitalier de Luxembourg, it’s a “real revolution.”
Today, blood cancers like leukaemia, lymphoma, and myeloma are often treated with chemotherapy, radiation therapy, stem cell transplants, or immunotherapy. The use of CAR-T cells, immune cells that are modified to recognise and attack cancer cells, fall into this last category, with the US Food and Drug Administration granting its first two approvals in 2017.
The Centre Hospitalier de Luxembourg in February announced the first CAR-T cell authorisation in myeloma patients here in the grand duchy, which comes after the treatment was first offered to patients for leukaemia and lymphoma in 2024. “It’s a real revolution,” says Sébastien Rinaldetti, a haemotologist, oncologist, and clinician-scientist at the CHL. “The CAR-T cells are a first-in-kind treatment that are able to give a long-lasting cure in 30-40% of heavily pretreated patients with acceptable side effects.” These side effects, which include cytokine release syndrome (characterised by fever and chills and also seen during COVID-19 infections) or neurological symptoms, are manageable, he pointed out.
“It’s the first time in history that we are using ‘living drugs,’” he said. “Cell therapy also existed before, through bone marrow transplantation, but these [cells] had never been manipulated. When you are manipulating the cells, they are officially called drugs. So it’s the first time that we are using ‘living drugs.’ It’s quite a new experience for us. These drugs are very complex; this is not only a molecule like an antibody, or a small chemical product, like with conventional drugs. This is a whole, living, autonomous cell that can be manipulated in a lot of ways.”
How the process works
The process of creating CAR-T cells involves many steps. First, a patient is connected to an apheresis machine, which you might have seen if you’ve ever donated blood at a hospital or at the Red Cross. This apheresis machine allows for the collection of specific components of blood, like platelets or plasma, then returns the rest of the blood to the person.
In this case, T-cells, white blood cells that are part of the immune system, are isolated, collected, and sent to a manufacturing facility at a pharmaceutical company, explained Rinaldetti. There, in the facility, the patient’s T-cells are genetically modified by inserting a specific gene into cells. Because genes give instructions to cells on how to produce different molecules, this gene allows the T-cells to generate a specific receptor on their surface that helps them recognise cancer cells.
Need a visual? Imagine the T-cells as spheres which, thanks to the gene modification, can now grow little “antennas” on their surface that allow them to scan their environment and identify cancer cells by recognising certain characteristics. “It’s an ability they had lost,” Rinaldetti noted, but the modification gives them back this ability.
These T-cells are now called CAR-T cells, where “CAR” stands for chimeric antigen receptors – those “antennas” that can now grow on the surface of the T-cells. The pharmaceutical company multiplies these CAR-T cells, conducts rigorous quality checks, then ships them back to the certified facility, in this case, the National Centre for Haematology and Oncology at the CHL, the only centre in Luxembourg and one of the first centres in the Greater Region. The patient then gets their cells back, which multiply in the blood system, recognise cancer cells, and combat the cancer.
“Quite good response rates”
CAR T-cells provide a specific, targeted, personalised therapy option that only needs to be given once. “We have quite good response rates: more or less 30-40% of patients have long-term responses,” said Rinaldetti. “These CAR-T cells, which represent a one-time infusion [rather than multiple treatment sessions], can last dozens of years if everything goes well.”
But it doesn’t always work. “The problem is, with a high number of patients, the CAR-T cells die in a more or less short period of time, let’s say, weeks to months, and they are patients that do not respond to the treatment. So the challenge is to identify the mechanisms that are needed to give the cells the opportunity to persist for decades.”
An inter-disciplinary solution
Beyond using CAR-T cells to treat blood chancers like leukaemia, lymphoma, and myeloma, there are opportunities to develop cell therapies for solid cancers. “The micro-environment of solid tumours is very hostile to cell therapy, so they are trying to find solutions,” said Rinaldetti.
There’s also the possibility of modifying other types of immune cells, like natural killer (NK) cells, to use in therapies. “A really good thing for patients would be an off-the-shelf product. This would be possible if we could use NK cells,” he added. “By having off-the-shelf products, we wouldn’t need to do apheresis with each patient. We would immediately have the product available.”
In addition, CAR-T cells are not just for cancer: they’ve already been used, with “very good results”, to treat auto-immune diseases like lupus, said Rinaldetti. “I think the future of cell therapy and haematology will be a very inter-disciplinary road.”
Towards CAR-T cell production in Luxembourg?
Looking specifically at Luxembourg, there’s a lot of “room upwards” when it comes to research in the domain. “There’s no cell therapy research right now going on here, and this is something I want to change,” said Rinaldetti.
Because CAR-T cells interact with many different elements, it can be difficult to determine their fate. “In order to have successful implementation of this cell therapy, we need a very comprehensive understanding of cell-cell interactions and of the immune micro-environment.” Large amounts of data would need to be collected and analysed, which could then be used to create a “digital twin.” Digital twins are often seen in industry – like in prototype manufacturing – and give designers and engineers the opportunity to test different scenarios.
But “such an approach has been largely overlooked, resulting in a gap of CAR-T cell potential versus its actual effectiveness,” said Rinaldetti. “This digital twin would enable us to produce our own GPT platform – generative pre-trained transformer, like with ChatGPT – based on all the data we would gather with the multi-platform analysis. This would allow us to do our own design of CAR-T cells here in Luxembourg.” Today, the pharmaceutical companies that are responsible for this step of the process are in Belgium, the Netherlands, and the US, for example. Generating CAR-T cells locally, he pointed out, would also decrease the costs.
Rinaldetti also called for the establishment of a facility certified under Good Manufacturing Practices (GMP) for CAR-T cells in Luxembourg, which he argued would transform the country’s biotech landscape and keep it competitive. “It would bring wind under the wings and be an unprecedented opportunity for our biotech landscape to do cell therapy ourselves.”
