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Bacteria as a GPS Beacon for Tumor cell Therapy

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  • There’s a saying that the enemy of my enemy is my friend. That very well describes a cancer-fighting therapy scientists are exploring.  We’ve known that bacteria can penetrate and colonize human tumors which makes sense that scientists are engineering bacteria to carry a cancer-fighting tool inside tumors. Except, they’re using a bacterium that normally causes disease in humans: E. coli. But in this case, researchers engineered an E. coli strain called Nisle nineteen-seventeen which colonizes tumors.  

    Once the colonizing begins, the E. coli strain produces and releases a specialized antigen, a protein that binds to the surface of the tumor cell.  The other end of the protein contains the sequences for something called green fluorescent protein or GFP which is exposed on the surface of the tumor cells.  The GFP serves as a beacon drawing the attention of the body’s immune cells. Next, they removed the patient’s T-cells and engineer them to carry a new protein molecule on their surface called a chimeric antigen receptor.  

    The receptor is designed to recognize the GFP, the beacon the E. coli placed on the tumors, and kill those cells whether they’re at the primary site or have metastasized to other parts of the body.  The therapy works in mice with colon and breast cancer, but human tumors may be more difficult to penetrate. If the therapy works in humans, it could become a highly precise and effective tool against cancer.   

    We are Drs. David Niesel and Norbert Herzog, at UTMB and Quinnipiac University, where biomedical discoveries shape the future of medicine.   For much more and our disclaimer go to medicaldiscoverynews.com or subscribe to our podcast. Sign up for expanded print episodes at www.illuminascicom.com or our podcasts at:  Medical Discovery News (buzzsprout.com) 

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Probiotic-guided CAR-T cells for solid tumor targeting
Immunotherapy has proven highly efficacious for certain types of blood cancers, but the lower success rates for solid tumors remain a challenge. Vincent et al. designed probiotics that could home in and colonize solid tumors to improve chimeric antigen receptor (CAR) T cell immunotherapy. The two-step approach involved engineering a nonpathogenic strain of Escherichia coli, which delivered synthetic antigens to the tumor microenvironment and “tagged” the tumor (see the Perspective by Bressler and Wong). They next generated CAR T cells that were programmed to recognize these synthetic antigen tags. When the E. coli probiotic was administered, the CAR T cells could be directed to the solid tumors, where they orchestrated tumor cell killing in experimental models of breast and colon cancer. 

Engineered Probiotic Bacteria Colonize Tumors, Attract CAR-T Cells
Researchers at Columbia University have developed a probiotic-guided chimeric antigen receptor (CAR)-T platform that uses engineered bacteria to infiltrate and produce synthetic antigen targets, enabling CAR-T cells to find, identify, and destroy tumor cells in situ. The results of in vivo preclinical tests suggest that the combined ProCAR cell therapy platform could expand the scope of CAR-T cell therapy to include difficult-to-target solid tumors.

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