A nanoparticle RNA vaccine that takes advantage of the immune system’s response to viral infection and refocuses it to fight cancer is reported online this week in Nature. The study shows that the vaccine induces antitumour immune responses in mouse tumour models and three patients with advanced melanoma, and possibly represents a step towards a universal vaccine for cancer immunotherapy.
Ugur Sahin and colleagues targeted immune system cells called dendritic cells in mice by using an intravenously administered vaccine made up of RNA-lipoplex nanoparticles - RNA surrounded by a lipid (fatty acid) membrane, similar to a cell membrane. They find that adjusting the net electrical charge of the nanoparticles to be slightly negative is enough to efficiently target dendritic cells. The lipoplex protects the RNA from being broken down by the body, and mediates its uptake into dendritic cells and macrophages in the spleen, lymph nodes and bone marrow, where the RNA is then translated into a cancer-specific antigen.
The authors show that this triggers a strong antigen-specific T-cell response and mediates a potent interferon-α (IFNα)-dependent rejection of progressive tumours in several mouse tumour models. In preliminary results from a human phase I dose escalation trial of the vaccine, the authors show that three melanoma patients treated at a low-dose level experience strong IFNα and antigen-specific T-cell responses. They conclude that, because almost any protein-based antigen can be encoded by RNA, the nanoparticle vaccine may potentially qualify as a universal vaccine for cancer immunotherapy.
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