University of Pittsburgh researchers have developed a novel approach to enhance skin immunization by targeting keratinocytes, the predominant cells in the epidermis. By manipulating the XBP1 pathway in keratinocytes, they have created a pro-immunogenic microenvironment that significantly increases immunogenicity. This innovative strategy could lead to more effective preventive and therapeutic vaccines against a broad range of diseases, including cancer and AIDS, without the adverse effects associated with traditional adjuvants.
Description
The novel approach involves over-expressing XBP1 in keratinocytes to improve antigen delivery and create a pro-inflammatory environment essential for immune induction. XBP1 is an ER-stress associated factor that regulates ER structure and function, influencing protein production and secretion, and cell differentiation and survival. This method enhances the production and secretion of pro-inflammatory cytokines and mediators, as well as a keratinocyte-expressed antigen, resulting in increased immunogenicity. This strategy is particularly relevant for genetic immunization, where plasmid DNA encoding antigen and XBP1 promoting factors can be delivered to keratinocytes to create a potent and long-lasting skin immunity.
Applications
• Preventive and therapeutic vaccines
• Genetic immunization
• Enhancing immune responses in the skin
Advantages
This approach targets keratinocytes to improve skin immunization, leveraging the natural XBP1 pathway to create a pro-inflammatory environment without the use of pathogen products or synthetic mimics. It has a potent adjuvant effect and is potentially enabling for non-viral skin-targeted genetic immunization. This method is expected to be well-tolerated and free from the adverse effects associated with traditional adjuvants.
Invention Readiness
The novel approach of engineering keratinocytes for enhanced skin immunization has been validated through in vivo studies. Researchers have successfully demonstrated that over-expressing XBP1 in keratinocytes leads to increased immunogenicity, with enhanced production and secretion of pro-inflammatory cytokines and mediators.
IP Status
https://patents.google.com/patent/US20220218821A1
