Much like an alarm clock wakes you up in the morning, the components in vaccines wake the immune system up and help guide it to develop protective immunity. While vaccines are canonically thought of in the context of preventing widespread illness, RNA vaccines can also be used as personalized medicine against aggressive diseases such as cancer. These therapeutic 鈥渃ancer vaccines鈥 work by priming the immune system to target tumor specific markers.
Modern RNA medicines 鈥 both vaccines and gene therapies 鈥 are delivered with a specialty delivery system. At present, the most advanced delivery system are lipid nanoparticles (LNP). When RNA medicines are meant to be vaccines, there is a requisite level of inflammation needed to achieve maximum effectiveness. However, other RNA medicines merely seek to deliver a critical enzyme coded as RNA, and here, inflammation can dampen efficacy and preclude repeated dosage. To increase the effectiveness of vaccines in a therapeutic context, we need a better understanding of what components in the vaccine specifically drive inflammation.
Now, new work from the Majumdar Lab published in ACS Nano finds that a key component of the LNP delivery system, the ionizable lipid, is responsible for driving much of the inflammation induced from vaccines that use a LNP delivery system. The authors find that the chemistry of ionizable lipids can be changed resulting in either inflammatory or non-inflammatory LNP delivery vehicles.
The results of this study provide a method by which vaccines for aggressive diseases such as cancer could be administered with a precisely tuned amount of inflammation to counter the cancer. In the future, the authors plan to map out a more in-depth analysis of inflammation causes by studying the interaction between the LNP delivery system and cell recycling machinery known as endolysosomes.
This study was made possible by trainees William Dowell, Jake Dearborn, Sylvester Languon, Zach Miller, and Tylar Kirch, and is the result of collaboration with Matt Poynter PhD, Michael Toth PhD, Kalev Freeman PhD and Jon Boyson PhD. This work was supported by a 日韩无码 Cancer Center Pilot Grant, and NIH grant P20GM125498.
You can read the full study .