Identifies and Eliminates Specific Enzymes that Cause Cell Growth in EBV-Associated Cancers
This dual targeting agent reactivates the Epstein-Barr virus (EBV) to treat cancer patients by targeting enzymes that support the EBV latent state and thereby, uncontrolled EBV-cancer cell growth. The Epstein-Barr virus is a human herpesvirus infecting most humans. It is one of the two members of the gamma-herpesvirus family known to cause cancer in humans, infecting B cells of the immune system and epithelial cells. Once EBV’s initial lytic infection is brought under control, EBV latency persists in the individual’s B cells for the rest of their life. Most people become infected with EBV and gain adaptive immunity. In the United States, about half of all five-year-old children and about 90% of adults have evidence of previous infection.
EBV is associated with various non-malignant, premalignant, and malignant lymphoproliferative diseases, such as Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma, post-transplant lymphoproliferative disease/lymphoma, nasopharyngeal cell carcinoma, and gastric carcinoma. Lymphomas are among the most common blood cancers in the United States, with over 80,000 new cases of Hodgkin’s and Non-Hodgkin’s lymphoma diagnosed annually. Oncolytic therapies destroy cancer cells by purposefully reactivating the lytic phase of EBV resulting in cancer cell death directly and indirectly through the genomic incorporation of an antiviral. Molecules that induce the lytic phase of EBV include DNA methyltransferase inhibitor, immunoglobulins, and HDAC inhibitors. Current therapies rely heavily on pan-HDAC inhibitors, which non-selectively block many enzymes, leading to significant toxicity, resistance, and limited long-term efficacy.
Researchers at the University of Florida have developed a dual targeting agent to selectively degrade HDAC3 and HDAC8-- enzymes directly linked to the viral latent state and therefore lymphoma progression. By guiding these enzymes to the cell’s natural recycling system for complete removal, the targeting agent delivers deeper, selective, and longer-lasting therapeutic effects with the potential for fewer side effects and improved patient outcomes.
Application
Targets enzymes, HDAC3 and HDAC8, to reactivate the Epstein-Barr virus in cancer cells for targeted and improved treatment
Advantages
- Targets HDAC3 and HDAC8, avoiding the broad toxicity of pan-HDAC inhibitors
- Works by removing the proteins with PROTAC technology instead of just blocking them, giving longer-lasting effects than current therapies
- Effective at low concentrations, saving time and cost in experiments while giving reliable results
Technology
This oncolytic dual-targeting agent is a next-generation protein degrader targeting HDAC3 and HDAC8. These enzymes help control and determine the genes expressed and active in cancer. Instead of simply blocking enzyme activity for a short time, the targeting agent guides HDAC3 and HDAC8 to the cell’s natural recycling system and tags them for removal. Rather than blocking the enzyme, it deletes it completely. By clearing the proteins from the cell, it delivers deeper and longer-lasting control with the potential for fewer off-target effects and less resistance.
Brochure
