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Cancer: A new mRNA vaccine eliminates tumors and prevents recurrences in mice

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Although the search for cancer vaccines has benefited from a storm of interest in recent years, it has struggled to develop. Using lipid nanoparticles that target 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 its recurrence.

On the one hand, messenger RNA (mRNA) vaccines currently used in clinical trials have been reported to induce side effects in the liver, which could be caused by the undesired expression of antigens in this organ. While these antigens can still induce an immune response, the risk of inflammation and liver damage remains.

On the other hand ” 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 Jinjin Chen, a postdoctoral fellow at Tufts University and co-author of the study, said in a statement. ” This cancer vaccine elicits a much stronger response and is able to carry mRNA of both small and large antigens “.

In fact, the mRNA vaccine presented in the study specifically targets the lymphatic system, where B and T lymphocytes and other immune system cells are “trained” to fight infection. Immunity to a cancer antigen (in the case of cancer) is acquired in the lymphatic system.

Delivery of lipid nanoparticles and targeting of the lymphatic system

Like Pfizer’s and Moderna’s COVID-19 vaccines, this potential cancer vaccine delivers mRNA in tiny lipid sacs (fat molecules) called “lipid nanoparticles.” These then fuse with the body’s cells when they reach the lymphatic system, allowing them to decode the mRNA and produce viral antigens – small fragments of the virus – that activate the immune system.

What we are 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 vesicles (and other additives) until they can target the organ of interest. For this study, they found lipid nanoparticles that accumulate in the lymph nodes (about three out of four) after they were injected subcutaneously into mice.

40% of subjects in complete remission, without recurrence

Targeted administration of the mRNA vaccine elicits robust CD8+ T cell responses that show excellent protective and therapeutic effects on the melanoma of interest ‘ the authors report. Mice with metastatic melanoma 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.

Furthermore, all of the mice in complete remission prevented the formation of new tumors when subsequently injected with metastatic tumor cells, demonstrating that the cancer vaccine was able to create excellent immune memory.

Source: Proceedings of the National Academy of Sciences

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