Alongside their success in Covid-19, RNA vaccines represent immense hope in the fight against cancer. Throughout the world, many projects have been launched to try to develop an injection that could overcome tumors and their metastases. So far, the results are not satisfactory enough. About twenty clinical trials have already been launched, but most come up against the same problem: a large part of the injected RNA arrives in the liver, an organ that is not conducive to a good immune response (in addition to the risk inflammation of the liver). The goal is to direct antigens to the lymphatic system where lymphocytes (white blood cells) and T cells are concentrated to learn how to fight off an outside infection. This is a challenge that the Tufts School of Engineering (United States) has managed to meet, where a team has developed a vaccine with very interesting results. Results published in the specialized journal PNAS.
Vaccines consist of reproducing a small portion of messenger RNA, that is to say a genetic code that corresponds to cancer antigens. This portion of RNA will create antibodies in the body of the vaccinated patient. By inoculating the patient with it, the vaccine provides the body with a kind of instruction manual for making small, harmless cancer targets on which the white blood cells can train before destroying the real tumor.
For its work, the Tuft School of Engineering performed its experiments on mice with metastatic melanoma. And the performance of the vaccine was impressive, since the tumors were significantly inhibited. In addition to this, 40% of the mice showed complete remission, with no tumors and no long-term recurrence when additionally given an existing treatment (which prevents the tumors from suppressing the immune response). The results suggest that the vaccine resulted in excellent immune memory because even after injection of metastatic tumor cells, no new tumors formed in mice in complete remission.
Target the lymphatic system
Alongside their success in Covid-19, RNA vaccines represent immense hope in the fight against cancer. Throughout the world, many projects have been launched to try to develop an injection that could overcome tumors and their metastases. So far, the results are not satisfactory enough. About twenty clinical trials have already been launched, but most come up against the same problem: a large part of the injected RNA arrives in the liver, an organ that is not conducive to a good immune response (in addition to the risk inflammation of the liver). The goal is to direct antigens to the lymphatic system where lymphocytes (white blood cells) and T cells are concentrated to learn how to fight off an outside infection. This is a challenge that the Tufts School of Engineering (United States) has managed to meet, where a team has developed a vaccine with very interesting results. Results published in the specialized journal PNAS.
Vaccines consist of reproducing a small portion of messenger RNA, that is to say a genetic code that corresponds to cancer antigens. This portion of RNA will create antibodies in the body of the vaccinated patient. By inoculating the patient with it, the vaccine provides the body with a kind of instruction manual for making small, harmless cancer targets on which the white blood cells can train before destroying the real tumor.
For its work, the Tuft School of Engineering performed its experiments on mice with metastatic melanoma. And the performance of the vaccine was impressive, since the tumors were significantly inhibited. In addition to this, 40% of the mice showed complete remission, with no tumors and no long-term recurrence when additionally given an existing treatment (which prevents the tumors from suppressing the immune response). The results suggest that the vaccine resulted in excellent immune memory because even after injection of metastatic tumor cells, no new tumors formed in mice in complete remission.
Target the lymphatic system
The reason the Tuft School of Engineering vaccine showed such encouraging results is because the team developed a new envelope to deliver the RNA into the body. Just like the RNA vaccines against Covid, the RNA is coated in a small bubble of lipids (a molecule of fat) which melts into the cells of the body. This is where our cells can”lire“the RNA code and produce antigens that will activate the immune system. The particularity of this vaccine is that it is delivered via nanoparticles capable of concentrating on the lymphatic system.
The latter includes the lymph nodes that often swell during an infection. This is where immunity is acquired. The lymph nodes are a bit like the “B and T cell training camp” against an enemy. Their “instructors”, dendritic cells and macrophages, which introduce antigens into B and T lymphocytes to activate them. With more vaccine going to the lymph nodes, the researchers found that the cancer vaccine was taken up by about a third of the dendritic cells and macrophages. A result far superior to conventional vaccines. The more dendritic cells and macrophages there are, the more B and T lymphocytes will be trained to kill cancer cells and the more powerful the body’s response will be against tumors.
Tailor-made lipid nanoparticles
To be sure that the RNA does indeed arrive in the lymphatic system, the researchers worked extensively on the chemical structure of the bubble of lipids in which the RNA is inserted as well as on the other components of the vaccine, until finding the formula which works. According to their suppositions, the lipid nanoparticles collect molecules on their surface when passing through the blood and that it is then these molecules which make it possible to bind to the receptors of the targeted organ, here the lymphatic system.
“Cancer vaccines have always been a challenge because tumor antigens don’t seem as “foreign” as those of viruses and bacteria to the eyes of the body. In addition, these tumors can actively inhibit the immune response“, explain Jinjin Chen, a postdoctoral researcher at Tufts University who is part of the research team. “This cancer vaccine evokes a much stronger response and is able to carry mRNA of both large and small antigens. We hope it could become a universal platform not only for cancer vaccines, but also for more effective vaccines against viruses and other pathogens..” The team had already worked on pathologies other than cancer. Genetic diseases, for which they tried to direct the RNA of vaccines into the brain, the liver or even the lungs. If it is perfected, this new way of coating and transporting DNA could be a game-changer. All that remains, before declaring victory, is to replicate these good results in humans.