Researchers at the University of North Carolina have recently discovered that activating an immune signaling pathway called STING can enhance the ability of genetically engineered T cells (CAR T cells) to eradicate breast cancer in mice. Originally, CAR T cells were used to fight against blood cancers like leukemia and lymphoma. However, they have been shown to be safe to use against solid tumors as well, provided that they’re coupled with other immunotherapeutic approaches.

CAR T cells weren’t able to cause significant tumor regression in solid tumors at first because they had to not only migrate into the tumor, but also survive long enough to kill the cells inside of it. To add a triple whammy, the tumor cells are typically immunosuppressive. So, they deactivate immune cells that come near them.

To deal with the survival part, the researchers used two different strains of T cells known as Th17 and Tc17, which are hardier and can survive longer in a tumor’s hostile microenvironment. For the immunosuppressive part, they used two small molecules named DMXAA and cGAMP, which both stimulate the STING immune response. cGAMP is the one that activates the human STING response, FYI. This resulted in the CAR T cells being able to survive longer and kill significantly more cancer cells, eventually destroying the entire tumor. Though here’s the catch: To make sure the cancer stays gone, the subjects have to be given anti-PD-1 and anti-GR-1 mAb in addition to the CAR-T and STING treatments. Thanks to these new steps, this treatment will go into clinical trials soon. After all, cGAMP is already being tested on its own. With every little advancement, more effective treatments begin to emerge. So, with cautious optimism, maybe we’ll be able to finally deliver the killing blow to several types of cancer within our lifetime.

For those interested in more detail, here is the article:

https://rupress.org/jem/article-abstract/218/2/e20200844/211644/STING-agonist-promotes-CAR-T-cell-trafficking-and?redirectedFrom=fulltext

A Triumphant STING

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