ICML 2023 | The role of Epstein-Barr virus in Hodgkin lymphoma pathophysiology

I started by telling you that it didn’t really matter the virus that we were targeting with these cells, but we made these cells specific for EBV so that they would not react against anything in the body. But actually, Hodgkin lymphoma is associated with EBV infection. We don’t know if all the cases are. They’ve started at some point related to the infection or just a fraction of the tumors that we see, but definitely in particular certain subtypes of Hodgkin lymphoma, like something called mixed cellularity Hodgkin lymphoma is frequently associated with infection by EBV. And we don’t think that it’s what we call a productive infection in the sense that it’s not you’re not going to be able to transmit the virus to someone else. But the virus has modified the B-cells in a way that actually makes them grow into a tumor. And so if actually the tumors that we’re treating, the Hodgkin lymphoma that we’re treating, they still have antigens from the virus, if they still express proteins of the virus, then it’s an extra benefit to use EBV specific T-cells to treat those patients. And so that is one potential advantage also of these cells. What we think EBV does in B-cells is to cause what we call a transformed cells. Essentially, it uses some pathways in, they hijack some pathways in the B-cells, usually virus only infects the cells, but what it tries to do is to make the most copies it can so that then it could go to other cells and infect them. So what happens is that when you trigger those genetic mechanisms, you can also cause genetic instability. And so you end up actually causing extra genetic problems in the cell. And so the cell, essentially, a normal cell becomes a tumor cell that then even if the virus disappears, the cell still has the genetic mechanisms that have been affected. And so it essentially just grows as a tumor and can cause a tumor. And so EBV has definitely been a virus that has been associated with the development of Hodgkin lymphoma.