A protein common on some types of cancer cell turns out to be the same one that in other circumstances allows the poliovirus to latch on to its host.
The discovery that the protein – known as CD155 – plays a role in both diseases has led to a leap forward in explaining earlier research that found that a modified poliovirus – the type used in the manufacture of vaccines – attacks tumour cells.
The ability of modified polioviruses to both attack tumour cells and simultaneously induce the body’s own immune response was first noted some years ago. It and several other modified viruses, including herpes simplex type 1, adenovirus and measles, are the subject of much research to determine their effectiveness at tackling brain cancer.
A 2016 book, Neurotropic Viral Infections, written by Dipongkor Saha of the Harvard Medical School and others, concluded that the field “has great promise as an avenue toward effective therapy for these deadly tumors”.
Despite the promise, however, the molecular process by which modified viruses attacked cancer cells has remained subject to conjecture – until now.
“We have had a general understanding of how the modified poliovirus works, but not the mechanistic details at this level,” says neurosurgeon Matthias Gromeier of the Duke University Medical Centre in North Carolina, US.
First, the poliovirus attaches to the CD155 protein, infecting and killing many tumour cells. This prompts the tumour cells to release antigens.
The immune system response to this is modified and amplified by the second stage of the poliovirus assault. The virus confronts dendritic cells and phages. The dendritic cells prompt T-cells to launch a defensive action against the polio-infected tumour cells.
The antibodies thus formed also latch onto and attack uninfected tumour cells – which until the polio invasion had been invisible to the body’s defences.
“This is hugely important to us,” says Gromeier.
“Knowing the steps that occur to generate an immune response will enable us to rationally decide whether and what other therapies make sense in combination with poliovirus to improve patient survival.”