Cancer vaccine prevents recurrence in mice

T cells attacking a cancer cell microscopic photo illustration T cells attacking a cancer cell microscopic photo illustration [ royaltystockphoto/Getty Images]

Scientists demonstrate a lipid nanoparticle (LNP) targeting lymph nodes endogenously, without the modification of any active targeting ligands, to develop an mRNA cancer vaccine. This method of targeting cancer in mice eliminated tumors and even prevented their recurrence.

This work is published in Proceedings of the National Academy of Sciences.

“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, PhD, Professor of biomedical engineering at Tufts School of Engineering. “Targeting the lymphatic system has helped us overcome many of the challenges that others have faced in cancer vaccine development.”

More than 20 mRNA cancer vaccines have been enrolled in clinical trials to date. However, much of the mRNA tends to end up in the liver. While antigens produced in the liver can still induce an immune response, there remains a risk of inflammation and liver damage. The response could be more effective and longer lasting if more of the vaccine were directed to the lymphatic system, where immune cells are concentrated.

Targeting is achieved by modifying the chemical structure of the lipids that make up the LNP. In this case, they found an LNP that concentrated in the lymph nodes after being injected subcutaneously into mice. Researchers believe that LNPs collect molecules from the bloodstream on their surface and that these selected molecules bind to specific receptors in the target organ.

The cancer vaccine in this study, similar to COVID-19 mRNA vaccines, also delivers mRNA into LNPs. The team explored an endogenous lymph node-targeting LNP named 113-O12B, which showed “increased and specific expression in the lymph node compared to LNP formulated with ALC-0315 – a synthetic lipid used in the COVID-19 vaccine Comirnaty”.

Targeted administration of the mRNA vaccine in this study “elicits robust CD8+ T cell responses, showing excellent protective and therapeutic effects in B16F10 melanoma. Notably, 113-O12B can efficiently deliver both full-length protein and mRNA encoded by short peptide-based antigens, providing a universal platform for mRNA vaccines.

Mice with metastatic melanoma that were treated with the lymph-targeting vaccine showed significant tumor inhibition and a 40% complete response rate – no tumors – with no long-term recurrence when combined with another existing treatment that helps prevent cancer cells from suppressing an immune response.

All mice in complete remission were prevented from forming new tumors when subsequently injected with metastatic tumor cells, showing that the cancer vaccine led to excellent immune memory.

“Cancer vaccines have always been a challenge because tumor antigens don’t always look as ‘foreign’ as antigens on viruses and bacteria, and tumors can actively inhibit the immune response,” said said Jinjin Chen, PhD, postdoctoral researcher at Xu’s lab. “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.

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