The Nobel Prize winning research surrounding immune checkpoint blockades takes one step further as Vanderbilt University bioengineers announce a major breakthrough. Investigators have designed a nanoparticle that can penetrate tumors and release a signal that tells them to start fighting.
“Checkpoint blockade has been a major breakthrough, but despite the huge impact it continues to have, we also know that there are a lot of patients who don’t respond to these therapies”, explained John T. Wilson, assistant professor of chemical, biomolecular and biomedical engineering. “We’ve developed a nanoparticle to find tumors and deliver a specific type of molecule that’s produced naturally by our bodies to fight off cancer”.
The molecule is called cGAMP, and is the main way to switch on the stimulator of interferon genes (STING) pathway, a natural mechanism employed to mount an immune response that can fight viruses, bacteria or eliminate malignant cells. cGAMP is delivered in such a way that it starts the immune response within the tumor, resulting in the generation of T-cells that can destroy the tumor from the inside and also improve responses to checkpoint blockade.
“Tumors are pretty conniving and have evolved many ways to evade detection from our immune system”, noted Dr. Wilson. “Our goal is to rearm the immune system with the tools it needs to destroy cancer cells”.
The initial work has focused on melanoma, but there are signs indicating that it may impact treatment for many other cancers, including breast, kidney, head and neck, neuroblastoma, colorectal and lung cancer.
One of the first obstacles was to design the right nanoparticle device, for which the team used “smart” polymers that respond to changes in pH specifically engineered to enhance the potency of cGAMP. It was after 20 or so iterations that a suitable vehicle was achieved, one that could activate STING efficiently in mouse immune cells, then mouse tumors and eventually human tissue samples.
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