Inflammasome Agonists for Vaccine and Immunotherapy

Background & Unmet Need

• Immunity is driven by two types of adaptive immune responses: the cell-mediated immune response (activated T cells) and the humoral immune response (activated B cells and antibodies)
• The generation of adaptive immunity depends not only on exposure to antigen, but also the context in which the antigen is encountered
• Adjuvants are substances that enhance an antigen-specific immune response when used in conjunction with the antigen
• However, traditional aluminum salt and oil-based adjuvants are often ineffective in boosting the immune response to therapeutic cancer vaccines or in immunocompromised individuals
• Unmet Need: Novel adjuvants that induce a strong adaptive immune response for both prophylactic and therapeutic vaccines

Technology Overview

• The Technology: Use of bacterial needle and rod proteins as adjuvants to activate the innate immune inflammasome pathway
• The Discovery: The bacterial proteins PrgI (Needle) and PrgJ (Rod) lead to robust activation of the inflammasome, a process that produces pro-inflammatory cytokines and acts as a mediator of adaptive immunity
• The inflammasome agonist effect was demonstrated in both human macrophages and dendritic cells
• PoC Data: Inflammasome activation led to the adaptive anti-tumor T cell immunity and priming of antibody production against tumor and bacterial pathogens
• The identified adjuvants may be directly delivered alongside vaccines or immunotherapies, fused to antigens and/or a TLR ligand, or genetically encoded for in vivo or ex vivo induction in dendritic cells

Technology Applications

• Adjuvants to enhance the host immune response to both prophylactic and therapeutic vaccines
• Cancer therapy via the use of chimeric target antibodies or activated dendritic cells to trigger immune response to tumor cells

Technology Advantages

• Adjuvants may be delivered directly alongside vaccines or applied to dendritic cells ex vivo
• Anticipated to deliver a stronger immunogenic effect than current aluminum or oil-based adjuvants