Immunotherapy is presented as the new hope once morest many cancers. Swiss research groups are finding ways to make it more effective. But their discoveries struggle to reach patients: the treatment authorization procedure is slow.
This content was published on February 12, 2023 – 08:15
Medical miracles can happen. Over the past decade, many patients with terminal cancer who have undergone experimental treatment with immunotherapy have seen their tumor disappear or go into remission. In short, immunotherapy offers “help to help yourself”. Instead of directly attacking cancer cells, as is the case with chemotherapy or radiotherapy, immunotherapy aims to stimulate and strengthen the patient’s immune system so that it recognizes cancer cells, destroys them or at least prevents their growth.
Clinical experiments and trialsExternal link have shown that cancer immunotherapy can prolong the life of patients, because their immune system learns to detect and attack cancer cells if they reappear. This “immunological memory” helps them live longer without cancer. Also, the therapy causes fewer side effects because it does not target all cells in the body, only the immune system.
Nevertheless, immunotherapies still fail in approximately two-thirds of cancer patientsExternal link. They can only act on certain types of tumours. Many people do not respond to immunotherapy at all, and if they do, the effects are temporary. Scientists are still wondering regarding the reasons for this failure. But, in Switzerland, a research group might have found a lead.
Towards a continuous marathon
One explanation is that T cells – a subtype of white blood cells that plays a key role in recognizing and attacking cancer cells – get overtired. They lose their ability to stop the progression of a tumour, while they identify and fight cancer cells. Known as “T cell exhaustion”, the phenomenon is one of the main obstacles to cancer immunotherapy. The problem of metabolic dysfunction means that T cells are depleted significantly faster than they can be regenerated, so they don’t have the ability to be transformed into effective cancer fighters, says Li Tang, associate professor in immuno-engineering at the Swiss Federal Institute of Technology in Lausanne (EPFL).
To revitalize exhausted T cells, researchers from Leman Biotech, an EPFL spin-off, have developed a booster protein that can be added to immunotherapy treatments. Li Tang, co-founder of Leman Biotech, humorously describes this mechanism as “metabolic T-cell fitness”. Currently, immunotherapies are stimulating T cells through different strategies and speeding up their metabolism to attack cancer cells, “just as a person is continuously offered Red Bull and caffeine to keep them running faster in a sprint of 100 meters, which exhausts him very quickly, ”explains Li Tang.
His team, on the other hand, is studying how to keep T cells cool and keep their metabolism in a balanced state, as if they were continuously running a marathon. The protein she developed contributes to this. Preclinical trials on miceExternal link showed an almost 90% cure rate when this protein was used in conjunction with the most popular forms of cancer immunotherapy, namely adoptive T-cell therapy and immune checkpoint inhibitors.
The most promising types of immunotherapy
Adoptive T cell therapy – also known as CAR-T cell therapy – boosts the natural ability of patients’ T cells to fight cancer. Immune cells are taken from the tumor and those that are most active once morest cancer are selected, grown in large quantities and reintegrated into the patient’s body.
Immune checkpoint inhibitors are drugs that allow immune cells to fight cancer more strongly by blocking immune checkpoint linkages. These are used to check whether a cell is abnormal or healthy. The artificial protein developed by the EPFL spin-off acts as a booster to improve therapeutic efficacy.
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From laboratory to clinic
Protein-boosting immunotherapy is just one of the recent advances in reorienting the immune system once morest cancer. According to a recent editorial published in the academic journal Nature CancerExternal link, there are currently dozens of approved immunotherapies and thousands of clinical trials underway in humans worldwide, with most trials involving solid tumors. Immuno-oncology, a $30 billion marketExternal link, continues to grow. But only a limited proportion of patients (from 15-30% in most solid tumors to 45-60% in melanoma for exampleExternal link) responds to immune checkpoint (ICI) inhibitors. Thus, many people therefore do not benefit from any improvement.
On the site clinicaltrials.govExternal linkwhich brings together information regarding past, ongoing and planned clinical studies worldwide, more than 800 CAR-T cell therapy trials are registeredExternal link, many of which are focused on solid tumors. However, only five CAR-T cell therapies have been approved by the US Food and Drug Administration for certain blood cancers, including leukemia, and 90% of treated patients relapse. No CAR-T cell therapy has yet been approved for solid tumors.
The development of cancer immunotherapy in Switzerland is similar to that in the United States, according to Pierre-Yves Dietrich, who heads the oncology department at the University Hospitals of Geneva. The professor points out that Swiss scientists also consider CAR-T cells and other types of immune cells to be the most promising therapeutic strategies once morest cancer.
So far, six CAR-T cell treatments have been approved by Swissmedic, the regulatory authority for therapeutic products. However, Alex Josty, spokesperson for Swissmedic, remains cautious regarding the concept and effectiveness of immunotherapy: Authorized CAR-T cell treatments are “intended to boost immunity, but this does not correspond truly to the established definition of oncological immunotherapy,” he notes.
Yves Dietrich stresses, for his part, that immunotherapy is only in its infancy and recalls that the first chemotherapeutic agents developed in the 1950s were not as effective as modern drugs. He expects the development of cancer immunotherapy to follow a similar slow curve, but remains optimistic. “New compositions and strategies will provide hope for years to come,” he says.
A careful…and slow approval process
Swissmedic observes a significant increase in applications for authorization of clinical trials of various immunotherapies, in particular trials with tumor infiltrating lymphocytes (TIL). Moreover, compared to the United States or Japan, which have mechanisms in place to speed up the review and approval process for CAR-T cell therapies, Swissmedic seems to be more cautious when it comes to to introduce such treatments into clinical trials. “Cancer immunotherapy drugs are very complex and high-risk products,” explains Alex Josty. During the authorization procedure, Swissmedic evaluates the preclinical test data very carefully and establishes the benefit/risk ratio for patients who suffer from an underlying disease and may have already received other treatments. .
In the meantime, Leman Biotech has managed to raise enough funds to start clinical trials and filed international patents for its new therapy. “We have already spent five years performing preclinical studies in mice to demonstrate feasibility,” Li Tang says. But, due to the complexity and length of the approval process, it will probably be several years before the protein developed by Leman Biotech enters the clinical phase in humans. Given these conditions, Li Tang and his colleagues plan to conduct the trials in China.
Yves Dietrich agrees that approval processes for cancer immunotherapies are complex in Switzerland, but manageable. “We have never had so many advances in such a short time, and this trend will continue over the next decade. The balance between patient protection and rapid access to new treatments is delicate,” he concludes.
Read and verified by Sabrina Weiss and Veronica DeVore / translated from English by Zélie Schaller
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