Oncolytic Viruses Attack and Kill Cancer Cells

Oncolytic viruses are "good" viruses that can specifically infect and kill cancer cells. Scientists at Luxembourg Institute of Health (LIH) are working on the development of new anticancer strategies and cancer treatments based on oncolytic viruses.

The rat virus H-1PV is an oncolytic virus able to selectively infect and kill cancer cells, inducing their disintegration (lysis). And that stimulates an anticancer immune response, without harming normal healthy tissues.

The LIH scientists have elucidated the mechanism through which the H-1PV cancer-destroying virus can attach to and enter cancer cells, thereby causing their lysis and death.

"[We] sought to elucidate the features of host cancer cells that enable oncolytic viruses to effectively infect and destroy them, focusing specifically on the factors required for cell attachment and entry," says research leader Antonio Marchini in a press release issued by LIT.

A research paper is published in Nature Communications. It indicates that laminins play an important role in how H-1PV kills cancer cells. Lamins are a family of proteins on the surface of a cancer cell to which this virus binds. They act as the 'door' through which oncolytic viruses enter cancer cells.

"Essentially, laminins at the surface of the cancer cell are the 'door' that allows the virus to recognise its target, attach itself and penetrate into it, subsequently leading to its destruction. In particular, the virus interacts with a specific portion of the laminin, a sugar called sialic acid, which is essential for this binding and entry process and for infection," explains researcher Amit Kulkarni.

The scientists identified 151 genes and their resulting proteins as activators and 89 as repressors of the ability of H-1PV to infect and destroy cancer cells. In laboratory tests, the scientists found that a gene called LAMC1 affects cancer cell resistance to virus-induced death in glioma, cervical, pancreatic, colorectal and lung carcinoma cells.

"These observations indicate that elevated laminin expression is associated with poor patient prognosis and survival in a variety of tumours, including gliomas and glioblastoma. The encouraging fact, however, is that cancers displaying high laminin levels are more susceptible to being infected and destroyed by the H-1PV virus and that patients with these tumours are therefore more likely to be responsive to this therapy," adds Marchini.

These findings have significant implications for the advancement of virus-based anticancer strategies. They also have implications for the prediction of a patient's response to this innovative therapeutic approach.

Further research could lead to the classification of cancer patients in terms of their sensitivity and responsiveness to H-1PV-based anticancer therapies. This will, in turn, allow the design of more efficient clinical trials with reduced costs and approval times. And, ultimately, this could lead to the development of enhanced cancer therapies.