Conditionally Replicating M. bovis for Treating Bladder Cancer and Tuberculosis

Background & Unmet Need

• The Bacillus Calmette–Guérin (BCG) vaccine is on of the most effective treatments for preventing tuberculosis (TB) and is formulated with a live attenuated strain of Mycobacterium bovis
• BCG administration has also been shown to be an efficacious treatment for bladder cancer, as the M. bovis bacteria triggers an immune response which also attacks cancerous cells
• However, live attenuated strains carry risk of infection in immunocompromised patients, and must be administered via the less-effective intramuscular route in TB vaccine patients
• Unmet Need: Method for precisely controlling the growth of M. bovis strains to avoid infection and enable alternative administration routes

Technology Overview

• The Technology: M. bovis BCG strains whose replication can be precisely controlled using a TetON/TetOFF system
• The TetON/TetOFF system either requires a tetracycline to grow (TetOFF) or are efficiently killed in the presence of tetracyclines (TetON)
• The inventors constructed and validated both TetON and TetOFF M. bovis strains
• PoC Data: The constructed double lysin TetON M. bovis BCG strain provided similar protection to wild-type BCG in a Mtb challenge study in mice but was rapidly eliminated in the presence of doxycycline
• Similarly, the constructed double lysin TetOFF M. bovis BCG strain induced faster bacterial death and is rapidly eliminated from immunodeficient mice in the absence of doxycycline

Technology Applications

• Development of a BCG vaccine for TB with reduced side effects
• Tunable alternative to M. bovis BCG strains currently used in bladder cancer immunotherapy

Technology Advantages

• TetON/TetOFF system allows precise control of conditions under which M. bovis bacteria can grow
• Allows to explore intravenous injection of BCG vaccine for TB immunization, which is likely more effective than the intradermal method
• Significantly reduces risk of infection in bladder cancer patients compared to current BCG vaccine