Lisa Roth, M.D., Director of Pediatric Oncology and an associate professor in pediatrics, medicine and pathology and laboratory medicine at Weill Cornell Medicine has been awarded a grant from the NIH National Cancer Institute for her study, “Targeting Latency Switch in EBV+ Lymphomas”.
Epstein-Barr virus (EBV) is a herpesvirus that infects B cells, the immune cells that make antibodies and that cause lymphoma when the cells grow uncontrollably. Many EBV-infected lymphoma cells are able to evade an immune response against EBV because the virus establishes a latent, or largely dormant, infection, restricting expression of its genes so that only one protein, which elicits a weak immune response, is expressed. In this study, Dr. Roth will develop a novel approach to the treatment of EBV-infected lymphomas by using drugs that affect gene expression to convert dormant virus in tumors to a more active state, thereby sensitizing resistant tumors to an anti-tumor immune response directed at EBV.
Dr. Roth and her team aim to develop a rational approach to the use of agents that affect epigenetic regulation of the EBV genes. Epigenetic regulation occurs by adding or removing chemical marks on DNA, thereby affecting whether a gene is switched on or off. The team will also determine which immune cells are required to eradicate these lymphomas, including their activation status and function, and will characterize the predominant viral protein fragments to which they are responding. Dr. Roth will also explore mechanisms of potential resistance to decitabine, a drug that affects epigenetic gene regulation and mediates the switch in viral activity. The team will also develop therapeutic combination strategies that maximize the percentage of cells that convert from a dormant to more active state. Lastly, they will establish therapeutic approaches that enhance the immune destruction of these lymphomas.
This work has implications beyond lymphomas to all malignancies in EBV-infected cells.