Deploying the full power of our immune system against cancer cells, to destroy them and cure the sick: the arrival of the first immunotherapy treatments in 2011 raised immense hopes. Previously convicted patients were saved, and the discovery won a Nobel Prize in 2018 for the scientists who first developed this new anti-cancer weapon. But, as powerful as they are, these treatments only work in a small number of patients: 40% to 50% in melanoma, 20 to 30% at best for other tumours. “The whole challenge today is to succeed in using the immune system in a larger proportion of patients. And therapeutic vaccination is one of the avenues that could help us do this”, explains Dr Stéphane Champiat, oncologist at Gustave-Roussy and author of “Immunotherapies” (Guy Trédaniel editions).
Therapeutic vaccination? As with vaccines against infectious diseases, patients are injected with a small piece of the pathogen against which they are to be protected, to teach their immune system to recognize and eliminate it. Here, however, it is not a virus or bacteria, but the patient’s own cancer cells, or rather a small part of their genetic material. “There has been research in this direction for decades, in vain. Now the context has evolved, and the hope that this strategy brings a benefit is there again”, confirms Professor Christophe Le Tourneau, head of clinical trials at Institut Curie.
The combination of two revolutions
First change, scientists have understood why vaccines did not work so far: because tumors know how to make themselves invisible to the immune system. So even by stimulating our defenses with a vaccine, there was no effect. However, immunotherapies marketed since 2011, precisely, make tumors visible to lymphocytes, the soldiers of our immunity. “This revives interest in the vaccine, which could be used in synergy with immunotherapy: on the one hand, we remove the brakes, and on the other, we push the immune system to act”, continues Professor Le Tourneau. . The second change has been highlighted by the health crisis: the emergence of new vaccine strategies, which make it possible to manufacture injections in record time.
Thanks to the combination of these two revolutions, oncologists could therefore soon see their arsenal enriched with a new weapon. Several laboratories have embarked on the race, and multiple trials are already underway. “Most experts believe that these vaccines will mainly serve to prevent relapses in patients previously treated for their cancer”, indicates Christophe Le Tourneau. Despite treatment with surgery, radiotherapy and chemotherapy, there may indeed remain tumor cells likely to relaunch the disease. The immune system, “educated” by the vaccine, would then eliminate them.
Cutting-edge technologies, and a bit of luck
Moderna, the American champion of anti-covid vaccines, announced promising data at the end of last year: a 44% reduction in the risk of relapse in patients operated on for advanced-stage melanoma and then treated with immunotherapy and a vaccine, compared to immunotherapy alone. Transgene, a French biotech, has also just presented preliminary results in head and neck cancers. Out of a dozen patients vaccinated after the removal of their tumour, none relapsed, compared to two in the control group. These are still only phase 2 trials, on very small numbers of patients, revealed for the moment through press releases. “This initial information is very encouraging, but we are now awaiting scientific publications to find out more”, insists Dr Stéphane Champiat.
Developing these therapeutic vaccines remains a high-flying exercise, which requires cutting-edge technologies and… a little luck. Once the patient’s tumor has been removed by surgery, its genome is sequenced. Scientists are looking to identify the mutations most likely to trigger an immune response. In the case of ENT tumors targeted by Transgene, for example, it involved choosing 30 mutations from an average of 3,000. For this, the French biotech has teamed up with a Japanese specialist in artificial intelligence. Its algorithm makes a pre-selection of 100 mutations, then the doctors retain 30, with which the Transgene teams manufacture the vaccine injected into the patient.
Results to be confirmed
After a careful examination of the white blood cells of the patients, it turned out that about ten of these mutations had indeed made it possible to trigger an immune response. “We were less likely to get there than to win the lottery: it’s really all the strength of AI to allow this result”, underlined Pr Jean-Pierre Delord, coordinator of the trial and doctor. at the Oncopôle de Toulouse, during a press conference. It now remains to show that this immune reaction effectively protects over time, then to confirm these results on more patients.
If the efficiency is there, manufacturers will also have to succeed in producing these hyper-personalized injections on a large scale. A big challenge. “This represents a huge industrial and organizational effort,” confirms Paul Burton, Moderna’s international medical director, to L’Express. The laboratory is currently planning to open platforms around the world to centralize patient samples and transport them to its Norwood site in the United States, where the vaccines will be manufactured. The question of production times is crucial: eight to ten weeks for Moderna, and three to four months for Transgene, which is in the process of expanding its production site in Strasbourg. The two laboratories ensure that they are working to further reduce these delays.
Many other questions remain open. Moderna uses messenger RNA vaccines, while Transgene uses a vaccine platform based on a genetically modified virus (closer to the technique used by Astra Zeneca and Johnson & Johnson against covid). Will the two technologies have similar performance, or will one be better than the other? Ongoing trials are targeting cancers with many mutations, which lymphocytes already attack naturally (but insufficiently). But this is not the case for all cancers: will these vaccines have a broad field of application or not? And if the effectiveness is confirmed, will it be sustainable? Will reminders be needed? Answering these questions will still take time: “We are only at the very beginning of this story”, sums up Paul Burton.