JEM: New combination strategies may be expected to enhance the effectiveness of breast cancer immunotherapy!

January 4, 2021 // -- In a recent study published in the international journal Journal of Laboratory Medicine, scientists from the University of North Carolina and other institutions found in mice that activating the most famous immune signaling paths that fight viral and bacterial infections may enhance the ability of genetically engineered T cells to remove breast cancer.
that CAR-T cells that can be used to treat specific types of cancer in humans, when combined with other immunotherapy, can also be effective in treating solid tumors.
photo source: © 2020 Xu et al. Originally published in Journal of Experimental Medicine. The chimeric antigen receptor T cells are a class of white blood cells that can be genetically engineered to identify and attack cancer cells that express specific proteins on their surface.
Now that researchers have been able to successfully treat patients with B-cell lymphoma with CAR-T cells, and they are currently conducting several clinical trials to treat many other types of blood cancers, car-T cells do not appear to be clinically active in solid tumor patients or animal models.
CAR-T cells are not effective against solid tumors because they have to migrate to the tumor and then survive long enough to kill all tumor cells.
addition, cells and molecules around tumors often have immunosuppressive effects that activate immune checkpoints to promote the inactivation of CAR-T cells. In the
study, researcher Serody and colleagues tested a variety of strategies in breast cancer mouse models to enhance the effectiveness of CAR-T cells, one of which was to use drugs such as cGAMP to treat mice that were able to activate STING paths in their bodies, an immune cell signaling pathline that normally induces inflammation of the body to respond to invading viruses or bacteria.
Activated STING pathlines can create an inflammatory environment in mouse tumors and improve the ability of CAR-T cells to accumulate and attack tumor cells, which increase when the car-T cells that produce immune signal molecule IL-17A are infused into the mouse body compared to CAR-T cells produced using standard techniques. 'We determined from our study that if therapeutic antibodies were used to treat mice, the attack of CAR-T cells in the body could last longer,' the
researchers said.
researchers found that when all methods were combined, tumors in the body's breasts in mice could be completely eliminated.
CGAMP is currently used in clinical trials to treat cancer patients, and several clinical trials are currently underway to use this method to suppress immunosuppressive cells in the body of patients with malignant diseases, and researchers are evaluating the therapeutic effects of combining CAR-T cells with immuno-checkpoint blockers in clinical trials, so the results of this paper may suggest a reliable strategy to enhance the activity and ability of CAR-T cells to attack solid tumors, said Serody, a researcher.
() Original source: Nuo Xu, Douglas C. Palmer, Alexander C. Robeson, et al. STING agonist promotes CAR T cell trafficking and persistence in breast cancer, Journal of Experimental Medicine (2020). DOI: 10.1084/jem.20200844