Virus-like particles (VLPs), based on the empty virus shell of rabbit calicivirus, have now been developed by University of Otago researchers to the point where they could be trialled to deliver anti-cancer vaccines and treatments in people.
Associate Professor Sarah Young, who was awarded a HRC Sir Charles Hercus Health Research Fellowship in 2008, says the VLP looks like a virus to the body’s immune system but it can’t replicate because it doesn’t have any genetic material inside it.
“We manipulate that shell of the virus and put on bits of the tumour and other immune-activating signals that will then be able to activate the immune system. The idea is to trick your immune system into thinking that its own tumour is like the virus.”
Dr Young says the work has involved close collaboration with virologist Professor Vernon Ward, who makes the VLP, and immunologist Professor Margaret Baird, who is an expert in
how the immune system is activated.
“The great thing about this calicivirus is that it acts differently to other VLPs; it enhances the killing arm of the immune response. It induces cytotoxic immune cells that specifically target and kill tumour cells.
“Other VLPs that are used in other vaccines, like the hepatitis B vaccine or the cervical cancer vaccine, target another arm of the immune response, which is to make lots of antibodies.”
The calicivirus-based VLP gets picked up by the dendritic cells. These cells then present it to the body’s killer T cells, which then attack the tumour.
Dr Young says one of the key features is the way they also form a memory response, just as you would see with the likes of a hepatitis vaccination.
“The whole idea with vaccination is that you’ve got these memory cells that will hang around your body for a very long time. If you were ever infected by hepatitis they would kill off those virally infected cells, before it did any damage to your body.”
Working on VLPs has been a long-term project for Dr Young. Her four-year $500,000 Hercus Fellowship allowed her to focus on putting certain immune enhancers on a VLP to activate particular types of cells within the immune system.
“A second paper we’re going to publish shows that you can put this enhancer molecule on the surface of VLP and inject it intravenously. It produces a strong anti-tumour response – much more than if you don’t have it.”
Dr Young says when it comes to fighting cancer they use the term vaccine more loosely. Instead of just being a prophylactic, given to prevent disease, they also use the term to
mean a therapy.
“The majority of the patients we want to treat would use it as a therapy. Once the patient has the disease we use the VLP to treat that patient and produce their body’s own immune response to that existing tumour.
“At the moment we are looking at how our VLP would fit in with the current gold standard therapy. Patients would come in and have a surgical resection or some chemotherapy: how would the use of a VLP work alongside that?”
In many ways the VLP works like chemotherapy in that it kills off tumour cells. However, the big advantage it has is that it shouldn’t have any side effects.
“Chemotherapy is often a blunt tool. It blasts anything that is growing. This is a very specific tool only targeting specific cells and providing that memory response.”
Dr Young says they are now at the stage where they can produce clinical grade VLPs that would be adaptable to different tumour models (e.g. melanoma and lung cancer).
“It works well in all of the settings we’ve tested it in so far. It could potentially be a universal treatment, which is really exciting.”
Dr Young says they are also looking at cellular therapy. This is where they grow T cells in the lab, put them back into the affected animal and then add the VLP later to boost the immune response of those T cells.
“You can do many different manipulations with this vaccine.”