Researchers from Vanderbilt University validated STING-NPs in freshly isolated human melanoma tissue and highlighted their potential to improve clinical outcomes of immunotherapy
A team of researchers from Vanderbilt University developed a nanoscale particle that penetrates tumor-infiltrating immune cells and flips on a switch that directs these cells to eliminate tumor cells. According to John T. Wilson, assistant professor of chemical and biomolecular engineering and biomedical engineering, tumors have evolved in different ways to evade detection from immune system and therefore, the objective of the research was to rearm the immune system with the tools it needs to eliminate cancer cells.
Checkpoint blockade is an effective approach against cancer. However, some patients do not respond to these therapies. The nanoparticle can find tumors and deliver a specific type of molecule that is produced naturally by the immune system to eliminate cancer cells. The molecule, 2′3′ cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), switches on the stimulator of interferon genes (STING) pathway, which is a natural mechanism used by the body to mount an immune response that can fight viruses or bacteria or clear out malignant cells. According to the researchers, the nanoparticle delivers cGAMP in a way that initiates the immune response inside the tumor. This in turn results in the generation of T-cells that can eliminate the tumor from the inside and can also improve responses to checkpoint blockade.
Although the research was focused on melanoma, the findings aid in the treatment of several cancers such as breast, kidney, head and neck, neuroblastoma, colorectal, and lung cancer, according to Wilson. The team initially developed the right nanoparticle with the help of ‘smart’ polymers that respond to changes in pH. After over 20 iterations, the team found one particle that can deliver cGAMP and activate STING efficiently in mouse immune cells, mouse tumors, and human tissue samples. The findings were reported in the paper: ‘Endosomolytic Polymersomes Increase the Activity of Cyclic Dinucleotide STING Agonists to Enhance Cancer Immunotherapy’, published in the journal Nature Nanotechnology on January 21, 2019.
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