It is a long-term bet, but which is beginning to give reasons for hope. Therapeutic vaccines to treat cancer are in full development and, among the pharmaceutical companies in the ranks, the Strasbourg-based Transgene believes in its chances. If viruses have a bad press, at Transgene, on the contrary, they are cultivated with care. Because it is on them that the researchers of this immunotherapy company are counting to attack the tumor cells.
Their strategy? Transform these viruses to produce tumor antigens, which will allow the immune system to activate and produce the appropriate response, in patients with cancer or at risk of recurrence. The viral vectors used by Transgene are from the vaccinia family, a virus close to smallpox. A return to the origins in a way: it was using this virus that the first vaccination was carried out by the British doctor Edward Jenner against smallpox, at the end of the 18th century.
Educate the immune system
“We know very easily how to modify it, to produce it on a very large scale”, explains Johann Foloppe, researcher at Transgene. Everything therefore starts in the vast biotech laboratories, near Strasbourg, with the production of the basic material, the viral vector. “We attenuate the virus, which will always be able to replicate, but we remove certain functionalities so that it replicates only in tumor cells,” said the scientist.
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It is engineering work, which reflects advances in gene therapy. It does not stop there: scientists will also arm this viral vector by providing it with additional functions to activate the immune system in cancer cells. Countless steps are then required to grow the vectors and verify their effectiveness. In the histology laboratory, scientists thus observe whether or not immunity is activated in tumor cells taken from patients. If all goes well, on their screens, cancer cells, represented in blue, are gradually covered with red or purple dots, which represent lymphocytes of cancer cells.
Therapeutic vaccines, which can use various technologies, such as messenger RNA, are of increasing interest to the world of research and biotechs. “They are based on the same principle: educating the immune system to spot abnormalities to which it does not react”, explains Professor Christophe Le Tourneau, head of the early clinical trials department at Institut Curie and principal investigator of a trial with Transgene. “A cell becomes tumor by modification of its DNA, these modifications are supposed to be identified, but they are not: it is necessary to make understand to the immune system, thanks to the vaccine, that they are dangerous”, adds the scientist.
Revolution for patients?
The sector is competitive: we find there in particular the American biotechs Moderna and German BioNTech, at the origin of the first anti-Covid-19 vaccines, also on therapeutic vaccine projects. The American company Dendreon has already marketed a treatment against prostate cancer. Transgene is working on several projects, including “TG4001”, in phase 2 trials on humans in cancers caused by a papillomavirus (or HPV). It is then a question of educating the immune system so that it recognizes and destroys cancer cells expressing certain HPV antigens.
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Biotech is also developing “myvac”, personalized vaccines, particularly in ovarian cancer. The drugs must again educate the patient’s immune system, but using genetic mutations specific to his tumor. To do this, it uses artificial intelligence, which will determine which genetic mutations to integrate into the viral vector.
On Monday, Transgene published the first positive results for a phase 1 clinical trial, showing that the immune system of the first patients treated had been activated. “Immune response does not mean clinical efficacy,” recalls, cautiously, Professor Le Tourneau. But the latter believes, however, that therapeutic vaccines could, in the long term, represent a revolution for patients.
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