If the search for cancer vaccines has benefited from a surge of interest in recent years, it is struggling to develop them. Using lipid nanoparticles targeted against the lymphatic system, researchers at the Tufts School of Engineering believe they have developed an effective mRNA cancer vaccine. The latter completely eliminated the tumor in 40% of the mice tested, while preventing their recurrence.
On one side, the RNA vaccines messenger (mRNA) currently used in clinical trials have been reported to induce side effects in the liver, which could be caused by the unwanted expression of antigens in this organ. While these antigens can still induce an immune response, there remains a risk of inflammation and liver damage.
On another side, ” cancer vaccines have always been a challenge because tumor antigens don’t always look as ‘foreign’ as antigens from viruses and bacteria, and tumors can actively inhibit the immune response “, said in a press release Jinjin Chen, postdoctoral researcher at Tufts University and co-author of the study. ” This cancer vaccine elicits a much stronger response and is able to carry mRNA of small and large antigens ».
Indeed, the mRNA vaccine presented in the study specifically targets the lymphatic system, where B and T lymphocytes and other cells of the immune system are “trained” to fight infection. It is in the lymphatic system that immunity against a cancerous antigen (in the case of cancer) is acquired.
Administration of lipid nanoparticles and targeting of the lymphatic system
Like vaccines against COVID-19 from Pfizer and Moderna, this potential cancer vaccine also delivers mRNA in tiny lipid bubbles (fat molecules) called “lipid nanoparticles”. These then fuse with the body’s cells on reaching the lymphatic system, allowing them to decipher the mRNA and produce viral antigens — small fragments of the virus — which activate the immune system.
« What we’re doing now is developing the next generation of mRNA vaccines using lipid nanoparticle delivery technology, with the ability to target specific organs and tissues said Qiaobing Xu, professor of biomedical engineering and co-author of the study. Targeting is achieved by altering the chemical structure of the lipids that make up the bubbles (and other additives) until they can target the organ of interest. For this study, they found lipid nanoparticles that concentrate in the lymph nodes (about three times out of four) after being injected subcutaneously into mice.
40% of subjects in complete remission, without recurrence
« Targeted administration of the mRNA vaccine elicits robust CD8+ T cell responses, showing excellent protective and therapeutic effects on the melanoma of interest “, report the authors. Mice with metastatic melanoma that were treated with the lymph-targeting vaccine showed significant tumor inhibition and complete remission in 40% of cases. There was no long-term recurrence when the vaccine was combined with another treatment to prevent cancer cells from suppressing the immune response.
In addition, all mice in complete remission prevented the formation of new tumors when subsequently injected with metastatic tumor cells, showing that the cancer vaccine was able to create excellent immune memory.