Synthetic Microbes (Excluding Oncolytic Viruses) for Immuno-Oncology Therapies

Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 2-4 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,250,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Current immuno-oncology (IO) therapies have provided valuable options for cancer treatment. However, many adult and pediatric patients, especially those with solid malignancies, do not initially respond to these therapies or later relapse after treatment. Barriers to existing IO therapies (e.g., immune checkpoint blockade and cellular immunotherapies) include poor tumor immunogenicity, antigen escape, limited tumor penetration, poor persistence of effector T-cells, hypoxic and immunosuppressive tumor microenvironment (TME), off-tumor effects, and systemic toxicities. Thus, there is an urgent unmet clinical need for innovative IO therapies that have the potential to address these challenges. The use of bacteria as a cancer treatment is not a new concept. Research has revealed that microbes possess inherent immunostimulatory properties and that some microbes have a natural ability to selectively colonize tumors due to the hypoxic and immunosuppressive conditions of the TME. However, the use of bacteria came with infectious complications and many patients died because of these side effects. For this reason, the idea of using bacteria against cancer waned with the advance of chemotherapy, radiotherapy, and other approaches. Recently, leveraging advances in synthetic biology and deeper knowledge about both microbiology and oncology, several studies have demonstrated the feasibility of engineering microbes towards safer and more efficacious outcomes such as selective delivery/guidance of immune-modulating chemotherapies and IO products including chimeric antigen receptor (CAR) T-cells into tumors and enabling TME changes to promote or enhance anti-tumor immunity. Therefore, synthetic microbes provide promising options for improving IO therapy outcomes by enhancing patients' response to treatment and by avoiding relapse.