Scientists have equipped a virus that kills carcinoma cells with a protein so it can also target and kill adjacent cells that are tricked into shielding the cancer from the immune system. It is the first time that cancer-associated fibroblasts within solid tumours – healthy cells that are tricked into protecting the cancer from the immune system and supplying it with growth factors and nutrients – have been specifically targeted in this way.
The researchers, who were primarily funded by the Medical Research Council (MRC) and Cancer Research UK, say that if further safety testing is successful, the dual-action virus – which they have tested in human cancer samples and in mice – could be tested in humans with carcinomas as early as next year. Currently, any therapy that kills the ‘tricked’ fibroblast cells may also kill fibroblasts throughout the body – for example in the bone marrow, lung (pictured) and skin – causing toxicity.
In this study, published in the journal Cancer Research, 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. This was designed to bind to two types of cell and stick them together. In this case, one end was targeted to bind to fibroblasts. The other end specifically adhered to T cells. This triggered the T cells to kill the attached fibroblasts.
The scientists successfully tested the therapy on fresh human cancer samples collected from consenting patients, including solid prostate cancer tumours which reflect the complex make-up of real tumours. They also tested the virus on samples of healthy human bone marrow and found it did not cause toxicity or inappropriate T-cell activation.