Scientists have equipped a virus that kills carcinoma cells with a protein so it can also target and kill immunosuppressive stromal cells. According to the team from the University of Oxford, this is the first time that cancer-associated fibroblasts within solid have been specifically targeted in this way. Currently, any therapy that kills these fibroblast cells may also kill fibroblasts throughout the body—for example in the bone marrow and skin—causing toxicity.
In this study, published in Cancer Research yesterday, the researchers used a virus called enadenotucirev, which is already in clinical trials for treating carcinomas. It has been bred to infect only cancer cells, leaving healthy cells alone. They added genetic instructions into the virus that caused infected cancer cells to produce a protein called a bispecific T-cell engager.
The protein was designed to bind to two types of cells and stick them together. In this case, one end was targeted to bind to fibroblasts. The other end specifically stuck to T cells, which triggered the T cells to kill the attached fibroblasts.
"We hijacked the virus's machinery so the T-cell engager would be made only in infected cancer cells and nowhere else in the body. The T-cell engager molecule is so powerful that it can activate immune cells inside the tumor, which are being suppressed by the cancer, to attack the fibroblasts," explained first author Joshua Freedman, from the department of oncology.
"Even when most of the cancer cells in a carcinoma are killed, fibroblasts can protect the residual cancer cells and help them to recover and flourish. Until now, there has not been any way to kill both cancer cells and the fibroblasts protecting them at the same time, without harming the rest of the body, Kerry Fisher, who led the research, added. "Our new technique to simultaneously target the fibroblasts while killing cancer cells with the virus could be an important step towards reducing immune system suppression within carcinomas and should kick-start the normal immune process.
Image: A human colorectal adenocarcinoma showing the fibroblasts (brown) surrounding the cancer cells (blue), protecting them from the immune system. Image courtesy of Human Protein Atlas.