Cancer Vaccines Using Lipid Nanoparticle Delivered mRNA Seem Promising
Cancer vaccines work by instructing the immune system to attack a particular cell surface feature characteristic of cancer cells. Cancers tend to subvert the immune system and suppress its activities in and around tumor tissue, however, so improvements in the effectiveness of a vaccine, the degree to which it will rouse the immune system to action, are helpful. Here, researchers present an example of the way in which the present generation of new vaccine technologies can be applied to this goal in the development of improved cancer vaccines.
Researchers had previously designed lipid nanoparticles (LNPs) that targeted gene editing packages to various organs. 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.
The lymphatic system, which includes the familiar lymph nodes that often swell up during an infection, is an important target for vaccines, because that's where immunity against a foreign antigen, or in this case, a cancer antigen, is acquired. If one thinks of the body as a field of battle - against viruses, bacteria, parasites, and tumors - and the B cells and T cells as soldiers, the lymph nodes are the boot camp where the B cells and T cells are trained to be more effective against the enemy. A key element of that training is the participation of dendritic cells and macrophages that introduce the antigens to the T and B cells and help fire them up.
The cancer vaccine works by delivering mRNA, allowing the cells to "read" the mRNA and produce viral antigens, small fragments of the virus that activate the immune system. With more vaccine going to the lymph nodes, researchers discovered that the cancer vaccine was absorbed by about a third of the dendritic cells and macrophages. That's significantly more than obtained with conventional vaccines. Mice with metastatic melanoma that were treated with the lymph-targeted vaccine showed significant inhibition of tumors and a 40% rate of complete response - no tumors - with no recurrence in the long-term when it was combined with another existing therapy that helps prevent cancer cells from suppressing an immune response. All the mice that were in complete remission prevented any new tumors from forming when injected later with metastatic tumor cells, showing that the cancer vaccine led to excellent immune memory.