Despite expression of many immunogenic antigens by tumor cells, the immune system often fails to recognize or respond to them, as cancer cells utilize mechanisms that render the immune system tolerant. As such, anti-cancer immunotherapy is being developed treatment strategy to overcome tumor cells evading immune recognition and/or eradication. In this regard, the two main strategies include inhibition of tolerance-inducing T regulatory (Treg) cells and enhancement of immune-stimulatory Th17 cells. While various means have been explored, current approach to these parallel mechanisms have been limited in their efficacy, sometimes with concerns associated with gene delivery.
Immunostimulatory ligand with dual effect on pathways that regulate immune responses
Researchers at the University of Michigan have developed a novel immunostimulatory ligand (ISL) that shifts the immune balance from tolerance toward a Th17-polarized response. The data show inhibition of the activity of indoleamine 2,3 dioxygenase (IDO), a tolerance-inducing enzyme, which has been shown to be involved in both tumor and pathogen-associated tolerance. Additionally, the inventors have demonstrated that ISL triggers robust production of IL-6 in CD8- dendritic cells and IL-6 in Th17 differentiation. ISL has a dual effect on pathways that regulate immune responses: it inhibits a key tolerogenic enzyme that has been strongly implicated in immune evasion and stimulates production of a cytokine that has been previously shown to inhibit Treg and stimulate Th17 differentiation. Thus, ISL demonstrates a much desired immunostimulatory effect on two reciprocal arms of the immune response and is an excellent candidate for both cancer and infectious disease therapy.
Applications and Advantages
- Cancer immunotherapy
- Infectious disease therapeutic
- Potential adjuvant
- Prophylactic applications
- Immunostimulatory effect on both Treg and Th17 cells