Immuno-oncology

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Immuno-reprograming of the Tumor Microenvironment Using Synthetic Biotics

Wednesday, June 14
6:15 PM - 7:45 PM

The immunosuppressive milieu found within the tumor microenvironment has long been understood to be a key driver of tumor initiation and progression. More recently it has been appreciated that metabolites derived from biosynthetic pathways such as the tryptophan and adenosine pathways are major components in forming this immune privileged environment within the tumor. At Synlogic we are using synthetic biology in combination with natural probiotics to develop engineered bacteria or "Synthetic Biotics", which are programmed with exquisite precision to correct disease-causing metabolic dysregulation. Here we present results showing the development of two engineered bacterial strains that have been designed to consume either kynurenine or adenosine, two molecules known to play central roles in promoting tumor immune tolerance. In in vitro biochemical assays, the adenosine-consuming strain or the kynurenine-consuming strain were able to consume 180 and 80 uM adenosine or kynurenine respectively, within 2 hours. These levels of adenosine and kynurenine are ~100-fold and 20-fold higher respectively than the adenosine or kynurenine levels found in cancer patient tumors. For the kynurenine-consuming strain, this in vitro kynurenine consumption translated to in vivo activity where in sub-cutaneous CT26 tumor-bearing mice, the administration of this strain led to significant decreases in tumor kynurenine levels. Taken together these results demonstrate our ability to generate engineered bacteria that show significant in vitro and in vivo metabolic activity and support the further development of these synthetic biotics as potential immune-oncology therapies able to modulate the tumor microenvironment.

Kip West

Director, Pharmacology
Synlogic

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    Adam Fisher

    Synlogic

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      Vincent Isabella

      Synlogic

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        Katherine Walsh

        Synlogic

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          Binh Ha

          Synlogic

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            Mary Castillo

            Synlogic

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              Ashley Knight

              Synlogic

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                Yves Millet

                Synlogic

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                  Paul Miller

                  CSO
                  Synlogic

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                    Jose Lora

                    VP of Research
                    Synlogic

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