Viruses and mankind have shared an evolutionary history since the dawn of man, evolving, adapting to best infect and protect from one another respectively. They have the ability to enter the cells of any life form, inserting its viral DNA into the hosts genetic make-up and transforming the cell into its own personal factory, creating new editions of the pathogen.
This ability to reproduce anywhere has led to the pathogen becoming the most common biological entity according to some studies, allowing them to populate so to speak, every form of ecosystem on the planet.
When scientists mention the use of this type of pathogen in the treatment of certain conditions, it would be understandable to raise an eyebrow at the claim.
However, scientists from the Harvard Stem Cell Institute (HISC), part of the Massachusetts General Hospital, have recently published a report of such a collaboration with these infinitely small organisms in the treatment of brain cancer.
This study was published in the scientific journalJournal of the National Cancer Institute, led by Professor Khalid Shah, head of the Molecular Neurotherapy and Imaging Laboratory at the hospital.
However,similar methods have been utilized to study cancer treatment. Oncolytic virotherapy has been used before in clinical trials within medical sciences thanks to their preference to infect cancer cells, the beauty of this being visible following the breakdown of the infected cancer cell by the stimulation of the host’s own immune system, which releases more viral particles allowing further cancer breakdown.
The success of these trials however has had its ups and down, with very few studies showing significant results, the furthest of which have only reached Phase II of clinical trials.
The Harvard team were looking at ways of treating brain cancer, and had selected the herpes simplex in preclinical trials thanks to its affinity for entering dividing brain cells.
An extremely common pathogen, the herpes simplex is also known to cause cold sores and genital herpes, and ends up being a lifelong companion, and rarely results in visible symptoms.
Previous studies had also looked into using herpes as a method for cancer therapy. However, they stumbled on how to maintain the pathogen at the tumour site long enough for it to take effect.
The Harvard team seems to have been able to overcome this barrier.
The researchers used mesenchymal stem cells (MSCs) as viral carriers, using the fact that help keep the immune system response to a minimum when delivering the pathogen to its desired site. These stem cells typically turn into bone marrow when left to differentiate.
Once again, the ever faithful laboratory mice were used in the study, with the herpes-loaded MSCs injected into the tissue adjacent to the glioblastoma (brain) tumours of the animals via biocompatible gels, whilst others were given straight doses of the microbe
Shah explained during the news release that patients with these types of tumours typically undergo surgery in process known as debulking, where the cancerous tissue is removed. This process was replicated in the mice, removing the majority of the cancerous tissue. The pathogen was then injected in order to effectively mop up any remain cancer cells.
Using imaging proteins, they were capable of viewing the real time movement of the virus from the gel to the tumours and compared the results to those that were directly injected into the tissue.
The results from Shah’s team showed that the herpes stayed in the gel much longer than the free moving virus, keeping the stem cells alive and hence allowing adequate replication time. As a result, the efficacy of the simplex against the remaining cancerous tissue was much higher, meaning the team addressed one of the shortcomings of previous studies, which neglected to track the fate of the virus following injection, explained Shah.
The mice that were given the gel injection, instead of only receiving the pathogen, survived longer.
The study also looked into how to overcome cancer cells that occasionally resist the therapy. To do this, the herpes was engineered to express tumor-killing agent, called TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), that has the benefit of only reacting to tumour cells, keeping normal tissue healthy.
Using the same mouse model, the team saw an increased survival rate in the animals which underwent the procedure.
Shah went on to mention how their study has helped overcome some of the challenges of current studies whilst providing hope for the effectiveness of this treatment in other types of tumours as well.
How else would you like to see virotherapy used in modern medicine?