Targeting lymph nodes
Researchers at Tufts School of Engineering have developed a method of targeting a vaccine that makes it so strong and accurate that it eliminates tumors and prevents their recurrence.
The new vaccine contains mRNAs that penetrate the body's cells, allowing cancer antigens to be produced according to the instructions they carry. The resulting small fragments of cancer proteins activate the immune system. mRNA is delivered by lipid nanoparticles.
The authors suggested that the response to the vaccine could be stronger and longer if it acted in the lymphatic system, where B- and T-lymphocytes, as well as other cells of the immune system, concentrate and "learn" to fight unwanted intruders. Targeting the lymphatic system would help overcome the safety challenges that other laboratories have faced in developing cancer vaccines. To date, more than 20 anti-cancer mRNA vaccines have been involved in clinical trials, but usually most of the mRNA is retained in the liver. Antigens produced in the liver also cause an immune response, but in this case there is a risk of inflammation and damage to the liver.
Qiaobing Xu and his colleagues had previously developed lipid nanoparticles that successfully delivered gene editing tools to the brain, liver or lungs. Such precise targeting is achieved by changing the chemical structure of the lipids that form bubbles, as well as a cocktail of molecules that bind to specific receptors in the target organ. Now researchers have created lipid nanoparticles, which, when injected subcutaneously, are concentrated in the lymph nodes.
A key element in the formation of the immune response is the participation of dendritic cells and macrophages – "instructor cells" of the immune system, which introduce antigens into T and B cells and help activate them. When the vaccine accumulated in the lymph nodes, about a third of its amount was absorbed by dendritic cells and macrophages. This is significantly more than when using conventional vaccines. The higher the number of instructor cells, the more trained "soldiers" in the form of B and T cells that generate a powerful response against cancer cells carrying the antigen encoded in the vaccine.
In experiments, mice with metastatic melanoma were treated with a new MRNA vaccine targeted at the lymphatic system in combination with existing therapy that prevents the suppression of the immune response by cancer cells. All animals showed significant inhibition of tumor growth, and in 40% of cases – complete absence of tumors without recurrence in the long term.
All mice in which complete remission was observed, upon subsequent administration of metastatic tumor cells, avoided the formation of any new tumors, proving that the cancer vaccine led to the formation of a stable immune memory.
Thus, the new anti-cancer vaccine causes a much stronger reaction and is able to transfer the mRNA of both large and small antigens. The authors hope that the method of targeting carrier nanoparticles on the target organ can become a universal platform for other anti-cancer and antiviral vaccines.
Article J.Chen et al. Lipid nanoparticle-mediated lymph node–targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response is published in the journal Proceedings of the National Academy of Sciences.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Tufts University: New Targeted Cancer Vaccines Eliminate Tumors and Prevent Recurrence in Mice.