Modern vaccine design requires both the presence of a antigen, a portion of the pathogen being immunized against, in combination with an adjuvant, a molecule that is capable of triggering the immune response by signalling danger to the immune system. For almost a century the primary adjuvant used in vaccines has been Alum, aluminum salts, however previous data has shown adjuvant activity arising from the usage of statins, a class of drug used to inhibit enzymes in the cholesterol synthesis pathway. Initial testing of polar and nonpolar statin drugs revealed efficacy of non-polar statin drugs in increasing immune response to vaccines. By inhibiting the production of molecular precursors to cholesterol, statins inhibit the modification of key molecular switches belonging to the class of proteins known as GTPases, in particular Rab5.

Exploration of these molecules mechanisms showed that they don’t function via the traditional pathway of sensing pathogen associated molecular patterns (PAMPS) and inducing the pyrogenic response. Researchers demonstrated that the inhibition of endosomal processing proteins via statins increased the retention time of antigens in dendritic cells and therefore increased the magnitude of immune responses through the ability of dendritic cells to cross present to CD8+ and CD4+ T-Cells. The major significance of the ability of statins to induce adjuvancy is their ability to induce TH1-Cell type responses, which are crucial for cancer checkpoint therapies, and which is not induced by the traditional treatment using Alum. Testing in mice models showed increased survival and cancer surveillance ability when statin drugs were combined with anti-PD1 antibodies, the standard for cancer immune checkpoint therapy. Therefore statin drugs display a promising effect in cancer immunotherapy when combined with existing checkpoint therapy.

Written By: Nate Dempsey