4:16 PM
Apr 16, 2018
 |  BC Extra  |  Preclinical News

Synlogic engineers E. coli to treat solid tumors

Synlogic Inc. (NASDAQ:SYBX) presented a pair of posters at the American Association for Cancer Research meeting in Chicago showing that E. coli Nissle genetically engineered to promote T cell activity could help treat solid tumors.

Tumors can generate an immunosuppressive microenvironment through the production of metabolites, such as adenosine and kynurenine, that leads to T cell dysfunction and exhaustion. Therapies that enhance T cell activity within tumors by depleting adenosine or kynurenine -- such as indoleamine 2,3-dioxygenase (INDO; IDO) inhibitors that decrease kynurenine levels -- could increase immunotherapy efficacy while avoiding systemic effects.

The Synlogic researchers showed how the company's synthetic biology platform could serve as an immuno-oncology approach by engineering probiotic bacteria to metabolize immunosuppressive metabolites.

The team first used synthetic biology to genetically engineer E. coli Nissle to deplete adenosine (SYN-Ade) or kynurenine (SYN-Kyn).

In a mouse solid tumor model, intratumoral SYN-Ade or SYN-Kyn decreased tumor growth and increased survival compared with vehicle. Combining intratumoral SYN-Kyn or SYN-Ade with an intraperitoneal combination of anti-PD-1 and anti-CTLA-4 antibodies against cytotoxic T-lymphocyte associated protein 4 (CTLA4; CD152) further decreased tumor growth and increased survival.

In February, Synlogic reported preclinical data from melanoma mouse models showing that intratumoral SYN-STING, comprising E. coli engineered to activate transmembrane protein 173 (STING; TMEM173) by producing cyclic GMP-AMP (cGAMP), reduced tumor growth, increased total T cell numbers and activated effector T cells in tumor draining lymph nodes.

At AACR, the researchers also showed they developed an engineered combination strain of E. coli that both consumes kynurenine and produces cGAMP (SYN-STING:Kyn) in vitro. Synlogic VP of Research Jose Lora told BioCentury that the company thinks combining the two functions in a single strain could increase efficacy. The company plans to test the combination strain in animal models.

Synlogic was down $0.08 to $11.38 on Monday.

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