Researchers around the world have been working for years on developing vaccines against different types of cancer, but without much success. Now, Tufts School of Engineering researchers think they have found one that does work. They have devised a method of targeting cancer in mice with a vaccine that is so strong and precise, it eliminates tumors and even prevents their recurrence.
The cancer vaccine works similarly to COVID vaccines from Pfizer and Moderna that deliver mRNA in tiny lipid (fat molecule) bubbles that ultimately fuse with cells in the body, allowing the cells to “read” the mRNA and produce viral antigens, small fragments of the virus that activate the immune system.
The cancer vaccine also delivers mRNA in tiny bubbles, but the mRNA codes for antigens found in cancer cells, and the bubbles, called lipid nanoparticles, can zero in on the lymphatic system — where immune cells are ‘trained’ — so that the response is significantly more potent.
“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, a professor of biomedical engineering. “Targeting the lymphatic system helped us to overcome many of the challenges that have faced others in developing a cancer vaccine.” The research was reported in the journal Proceedings of the National Academy of Sciences.
More than 20 mRNA cancer vaccines have been enrolled to date in clinical trials, but usually much of the mRNA ends up in the liver. While antigens produced in the liver can still induce an immune response, there remains a risk of liver inflammation and damage. The response could be more effective and long-lasting if more of the vaccine were directed to the lymphatic system, where B cells, T cells and other cells of the immune system are concentrated and learn to fight off unwelcome intruders.
Xu and his team had previously designed lipid nanoparticles (LNPs) that targeted gene editing packages to the brain and liver, as well as gene therapy to the lungs to reverse a genetic condition in a mouse model. Targeting is achieved by modifying the chemical structure of the lipids that make up the bubbles as well as other additives until the researchers find a combination that prefers to go to the organ of interest. In this case, they found an LNP that concentrated in the lymph nodes after they were injected subcutaneously into mice. The researchers think the LNPs collect molecules from the blood stream on their surface, and those selected molecules bind to specific receptors in the target organ.
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