Nobel prize is a reminder of hurdles faced by advanced therapies in Europe

The Nobel Prize for Medicine 2025, has been awarded to Shimon Sakaguchi (Osaka University, Japan), Fred Ramsdell (USA) and Mary E. Brunkow (Institute for Systems Biology, USA), for their work identifying regulatory T cells (Treg) cells and the FOXP3 gene critical to their function.

“Our immune system is extremely powerful. We need to be able to fight off any possible microbe. At the same time, we need to not attack our own tissues and organs, and if we do, we see immune disorders. [Regulatory T cells] keep our immune system in check,” said Professor of Molecular Genetics and member of the Nobel Committee, Rickard Sandberg.

In effect, T cells responsible for fighting threats, such as harmful viruses and bacteria, can also mistakenly attack healthy cells with similar surface proteins, Treg cells keep them in check.

Treg cell therapeutics have not yet reached the clinic, but there are more than 200 clinical trials currently underway to treat diseases like asthma, inflammatory bowel disease and improve the success of organ transplantation.

Barriers to Treg therapeutics in Europe

In a paper, published in 2023, scientists working in this field wrote that the advanced therapy medicinal products (ATMP) regulation required new Treg-based therapies to show benefits beyond the existing standard of care. The authors observed:

“Pharmaceutical companies or other funding agencies may be reluctant to pursue further trial stages if there is a risk that the significant benefit threshold will not be met, and approval will not be granted.”

Although the European Medicines Agency (EMA) plays a central role in evaluating ATMPs, clinical trials are overseen by national competent authorities. According to developers, this fragmented oversight adds considerable complexity to the process.

Further challenges arise from the inclusion of medicinal products under the EU’s GMO legislation, originally intended for food and agriculture. Because implementation of this and other rules varies across member states, companies often select the most favourable jurisdictions—potentially introducing population bias into trials.

AGORA, an EU-funded consortium investigating blocks to ATMPs, also identified the diverse application of regulations on Good Manufacturing Practice (GMP) as “creating a severe barrier to the development and delivery of ATMP medicines.”

The long hard slog to a breakthrough

Like many scientific advances, there isn’t just one eureka moment, but a long journey with twists and turns, shaped by setbacks, developments in technology and perseverance.

In the early 1970s, it was Richard Gershon who first used the expression ‘suppressor T cells’ to describe immune cells that restrain, rather than help the body to eliminate an unwelcome intruder. Sadly, Gershon died at the early age of 50, leaving others to get to the bottom of this mechanism.

Momentum faltered in the 80s when a region of the genome thought to contain the gene for the suppressor T cells produced negative results. Daniel Davis notes in his book, The Beautiful Cure: The Revolution in Immunology and What It Means For Your Health, that at this point funding fell away and “suppression” became a dirty word. By 1992, a review in Immunology Today, concluded that: “No realm of immunology has less credibility than that of suppressor T cells.”

Sakaguchi, told Davis, that the “missing-gene episode” didn’t put him off, he was eventually able to identify the T cells that were esponsible for suppressing immune responses that, when unchecked, attack the body’s own tissues. These regulatory immune cells can help explain the mechanisms behind autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and certain cancers.

Fred Ramsden and Mary E. Brunkow carrying out research at a company called Immunex in 2003 discovered the FOXP3 gene that when switched on or off can determine whether a T cells boosts or dampens an immune response, it is thought to determine the activity of around 700 other genes. Davis describes it as “a master control gene”.

As the EU considers the future of research funding and its link to competitiveness, Tregs research show that the road to success is not always linear, or predictable; it also shows that getting advanced treatments into use requires the right regulatory environment.