Development of a Non-Inflammatory Anti-tumor Vaccine Adjuvant: Expecting no cytokine toxicity with application to immunotherapy

Hokkaido University (Japan) succeeded in the chemical synthesis and development of a functionally-defined cancer-suppressing nucleic acid adjuvant¹⁾ which does not induce excessive inflammatory cytokines. This new nucleic acid adjuvant activates only toll-like receptor 3 (TLR3), and does not activate other functional molecules (such as RNA/DNA sensors). This adjuvant has fewer side effects, and is expected to contribute to the development of anti-tumor immune vaccines in the treatment of cancer, bringing good prognosis to many patients.

Recognition of a pattern of microbial RNA by toll-like receptor (TLR) 3 and cytoplasmic RNA sensors promotes activation of innate immunity in dendritic cells,2) induces cytokine3) production, and activation of cellular immunity. Conventionally, double-stranded virus RNA (such as polyI:C) have shown strong anti-cancer effect, and have been considered as promising as vaccine adjuvants. However, clinical application has been abandoned due to side effects such as severe inflammation and cytokinemia. At this time, we have developed a TLR3-specific ligand4) with a specified structure and function by a chemical biology method, which has been shown to induce NK/CTL dependent anti-cancer activation in a mouse transplanted cancer model. Since this new TLR3 ligand does not activate cytoplasmic RNA sensors (molecules which detect virus RNA), nor does it induce excess inflammatory cytokine production, application in an anticancer vaccine as a non-inflammatory nucleic acid immunological adjuvant with fewer side effects. 1) Adjuvant: A substance which can increase the body’s immune function, also called as antigenic strengthening agent. 2) Dendritic cells: Cells which play a central role in the immune system. These cells have strong antigen-presenting capacity to activate helper-T cells, which can detect the existence of cancer cells. 3) Cytokines: Proteins released from cells which can transmit information between cells. 4) Ligand: A substance which specifically binds and activates a specific receptor cell. In this case, it applies to an RNA derivative which binds and activates TLR3.