Researchers say they have developed a method that simulates Epstein-Barr virus (EBV) infection, and the immune cells that are activated as a result can kill non-Hodgkin lymphoma cells efficiently.
The team made use of antibodies that exhibit a piece of viral protein. The antibodies contain binding sites that target molecules on the surface of lymphoma cells.
The researchers used genetic engineering methods to fuse protein pieces of EBV to the “rear” end of the antibody protein.
As exposure to EBV is common, many people already have memory T cells that can mount a rapid immune response upon a new encounter with this pathogen.
The antibodies attach to the cancerous B cells and are subsequently engulfed into the cell interior. There, the antibody protein is degraded, and the individual fragments are presented by molecules on the surface of the cancer cells.
As a result, the viral protein is also exhibited on the cell surface, thus making it look like an EBV infection to the immune system.
The researchers found that T cells effectively killed the “infected” lymphoma cells in vitro. In blood cells from individuals who had been infected with EBV in the past, the antigen-armed antibodies successfully activated memory T cells.
“This is a clear indication that our antigen-armed antibodies can also induce an immune response against lymphoma cells in a living organism,” said study author Henri-Jacques Delecluse, MD, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.
To activate the immune system in as many people as possible, Dr Delecluse and his colleagues also inserted larger pieces of EBV proteins into their antibodies.
Depending on a person’s genetic makeup, the cells could then cut out various smaller protein segments and present them on their surface.
“A problem with antibody-based cancer therapies is that the tumor cells make the surface molecule targeted by the antibody disappear from their surface,” Dr Delecluse said. “To prevent this situation, we used a mixture of antibodies that target 4 different B-cell surface molecules.”
For more details, see the researchers’ article in Blood.
