A new cancer immunotherapy approach uses nanoparticles carrying tumor RNA to target dendritic cells, leading to a strong anti-tumor response with antiviral-like features.
Researchers have been trying to develop vaccines to fight cancer for decades now, and it is now known to be more difficult than first thought. Cancer progression is not typically characterized by strong inflammatory signals that are necessary to initiate an immune response. Thus, most cancer vaccine strategies are aimed at directly activating a patient’s immune system. Since dendritic cells are extremely well suited at processing and presenting antigens for T cell activation, immunologists are currently working on developing vaccines that target these specialized antigen-presenting cells. Nanoparticles containing a tumor antigen and a dendritic-cell-targeting antibody have proven to be an effective strategy thus far.
Researchers at Johannes Gutenberg University recently developed a different type of nanoparticle that does not require ligands or antibodies to target dendritic cells . They found that manipulating the RNA-to-lipid ratio made the nanoparticles slightly negatively charged, which helped direct them to dendritic cells. By using RNA encoding a fluorescent protein, they were able to track the distribution of the nanoparticles when injected intravenously in mice. Fluorescence was observed in dendritic cells and macrophages in the spleen and other lymphoid tissues. Interestingly, they also observed interferon-α (IFNα) release by plasmacytoid dendritic cells and macrophages after nanoparticle injection. IFNα induced maturation of precursor dendritic cells, which then allowed them to migrate and encounter T cells in the spleen and lymph nodes. This event resulted in a strong effector and memory T-cell response, similar to that launched during an early systemic phase of a viral infection.
The researchers extended their findings to a phase I clinical trial in patients with melanoma. Three patients were injected with a low-dose level of nanoparticles carrying RNA encoding tumor antigens. All three patients produced IFNα and developed strong antigen-specific T-cell responses, involving both CD4+ and CD8+ T cells. CD8+ T cell activation is usually characteristic of an antiviral response, so having both types of T-cell responses may lead to robust and long-lasting antitumor activity.
Although the clinical trial is in its early days, the results are promising for cancer immunotherapy. At HemaCare, we are excited to hear about advances in the development of a cancer vaccine. We provide dendritic cells for your research purposes. Please call (877) 397-3087 if you have any questions or would like to place an order.
 Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature, doi:10.1038/nature18300 (2016).