Different therapeutic effects of modified oncolytic viruses


Using oncolytic viruses is a new strategy for cancer immunotherapy. To enhance the therapeutic effect the viruses can be modified with immunostimulatory factors. A study from IGP shows that the effect of such factors depends on the kind of oncolytic virus that is modified. To achieve the desired therapeutic benefits, careful consideration is therefore needed when choosing the virus. The study has been published in the journal Molecular Therapy Oncolytics.

A new method to treat cancer is to use oncolytic viruses. These are viruses that infect cancer cells where they replicate until the cancer cells burst and release new virus particles, that in turn can infect other cancer cells. When the cancer cells are destroyed this elicits an anti-tumour immune response, which contributes to the anti-tumour effect of the oncolytic virus.

Currently, several types of oncolytic viruses are developed for cancer therapy. In the present study, the researchers studied if the anti-tumour effect could be enhanced by arming the viruses with proteins that should stimulate the immune response. The results showed that distinct immune stimulation profiles are elicited when the same immunostimulatory factor is present in different oncolytic viruses.

“We armed two types of oncolytic viruses – vaccinia virus and Semliki Forest virus – with two immune activating proteins and studied the effect in a mouse model of the tumour type neuroblastoma. For the vaccinia virus the presence of the proteins resulted in an enhanced anti-tumour effect through the production of antibodies against the cancer cells. When we used the same proteins in the Semliki Forest virus, instead an immunological response against the virus was induced,” says Di Yu, who has led the study.

The study shows that careful consideration and detailed characterisation are needed when engineering oncolytic viruses with immune-modulators. In the case of Semliki Forest virus, which is very immunogenic by nature, the focus of engineering can be directed towards improving the virus’ ability to burst the cancer cells, inducing a direct viral lytic response. For vaccinia viruses, which by nature have immunosuppressive properties, the focus can be directed towards arming the virus with immune modulators to improve immune response against the cancer cells.

“Our conclusion is that if you want to engineer oncolytic viruses with immune modulating agents you should base the strategy both on the selected virus and on the targeted tumour type, to achieve the desired therapeutic benefits,” says Di Yu.

More information.
Article in Molecular Therapy Oncolytics
Di Yu’s research in Magnus Essand’s group