For the first time, scientists have equipped a cancer-killing virus with a protein that enables it to search and destroy the adjacent cancer-associated fibroblasts that are ‘tricked into' protecting the cancer cells from body's immune system.
Cancer-associated fibroblasts are found within solid tumours. They are the healthy cells which, by mistake, provide a shield to residual cancerous cells and protect them from being killed by the immune system. These fibroblasts also supply nutrients to cancerous cells and help them recover and grow in the body.
Although therapies are currently available to kill the tricked fibroblast cells, a big disadvantage of these therapies is that they may also destroy fibroblasts throughout the body, thus causing toxicity in the body.
The current study, involving scientists from the University of Oxford, focused on using the oncolytic group B adenovirus enadenotucirev, which has been found to have the ability to kill only carcinogenic cells in the body, thereby leaving healthy cells alone.
Scientists found that changing the genetic coding of the virus caused the infected cancer cells to create a protein named bispecific T-cell engager. This protein binds two types of cells - a fibroblast cell and a T-cell (an immune cell that kills defective cells in the body). The binding of these two cells then triggered the T cells to destroy the attached fibroblast cell.
"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," said Dr Joshua Freedman, from the University of Oxford and the first author of the study.
So far, scientists have tested the functioning of the modified, dual-action virus in human cancer samples and in mice. They are now planning to test the virus in cancer patients next year to find out whether it is safe to use the genetically modified virus in such patients.
The study was funded by the Medical Research Council (MRC) and Cancer Research UK, and the findings are published in journal Cancer Research.
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