British and Chinese researchers have genetically modified the Vaccinia virus (used for years in smallpox vaccines), making it capable of infecting and destroying cancer cells.
Infecting pancreatic cancer, one of the most difficult to fight, with a virus that can then destroy the tumour itself.
This cutting-edge therapy has been developed on an experimental basis by a group of researchers from Queen Mary University of London and Zhengzhou University (China), who published the results of their work in the Journal for ImmunoTherapy of Cancer.
About Vaccinia Virus
The virus in question is called VVL-21 and is one of the so-called oncolytic viruses, i.e. micro-organisms that cause lysis (cell rupture, with the consequent destruction) of certain types of cancer and that are also able to initiate a strong immune response against the tumour.
Since the 1960s several types of oncolytic viruses (adenoviruses, herpes simplex, measles virus and others) have been studied for their anti-cancer “powers”. But the results have almost always been unsatisfactory for various reasons, such as the excessive weakness or strength of the virus, the risks also for healthy cells and the ability of tumour cells to create resistance.
This time, however, the British and Chinese researchers achieved outstanding results by focusing their attention on the Vaccinia virus. It is the same one (in a weakened version) that has been used for decades as the main component of vaccines against smallpox (this is because it has a structure similar to that of the Variola Virus, which is responsible for smallpox, but most of the time does not cause serious damage to the body).
How does the therapy work?
The scientists genetically engineered the DNA of the Vaccinia virus, modifying the production of a protein (called B5R) to make it easier for VVL-21 to penetrate the pancreatic tumour. In addition, they added a gene to make the virus produce a substance known for its anti-tumour activity, namely interleukin 21 or IL21 (hence the name VVL-21).
The VVL-21 virus was administered to laboratory animals along with an anti-cancer drug (a PI3Kδ inhibitor, as it is called in technical terms). It immediately had a powerful effect against cancer cells, inducing their death and also changing the microenvironment around the tumour (i.e. removing the brakes that the tumour itself produces to inhibit immune system responses). Furthermore, treatment with VVL-21 made pancreatic cancer cells (which are usually quite resistant) sensitive to immunotherapy drugs called checkpoint inhibitors (another way of allowing the body’s defence system to return to functioning at its best against the tumour). For its part, the drug (the PI3Kδ inhibitor) prevented the immune system from taking action against the virus, hence creating a powerful synergy.
After a series of tests, the VVL-21 virus proved capable of reaching both the main tumour mass and metastases, and of greatly increasing the concentration of immune system “policemen”, such as CD8+ lymphocytes and Natural Killer lymphocytes in the areas surrounding the cancer cells.
The team of researchers is now working on starting a phase I trial (the first step in a long process) in humans as well. And if the results produced in animal models are also found to be positive in patients, within a few years the combination of the virus and immunotherapy could perhaps make a real difference to the statistics that place pancreatic cancer among the most dangerous cancers.
«The current prognosis for patients with pancreatic cancer has not improved for many decades», confirms Louisa Chard Dunmall, a researcher at Queen Mary University and joint first author of the study with her colleague Giulia Marelli, «and so we urgently require new treatments that can improve long-term survival. Our platform provides an exciting new mechanism of attacking the tumour in these patients».