Since the advent of cancer therapy, clinicians and patients have sought more targeted treatments that attacked tumors while sparing normal tissues. Several viruses, including the reovirus, or Respiratory Enteric Orphan virus, have shown a strong preference for killing cancer cells vs. normal cells. These oncolytic (tumor-bursting) viruses represent an entirely new approach to cancer treatment.
Calgary-based Oncolytics Biotech has recently reported encouraging results from a U.K. Phase Ia/Ib clinical trial with its Reolysin® oncolytic reovirus formulation in combination with radiation for patients with a variety of advanced or metastatic cancers. The rationale for the trial emerged after preclinical work demonstrated that the addition of radiation enhanced the cancer-killing ability of Reolysin. Interim results from the Phase Ia/b human study suggest this is true.
The study has treated 22 middle-aged and elderly patients with various tumor types to date. Patients were split into two groups that received either 20 or 36 Gy of radiation, along with escalating dosages of two to six injections of REOLYSIN into a target tumour. Tumors included melanomas and cancers of the colon, pancreas, ovaries, larynx, and other sites. No serious or dose-limiting side effects were noted. Although this safety study was not designed to show tumor shrinkage, investigators noted a positive trend towards efficacy. Of the 11 patients in the Ia study, three experienced significant partial responses. Three of the 6 patients who completed the Ib trial also responded to treatment. Typically, only 5% to 15% of patients with advanced cancer respond to conventional cancer treatments. These particular patients had cancers that either did not respond to cancer treatment, or for whom no other treatments were available.
Reovirus is a double-stranded RNA virus that causes asymptomatic human infection. When it encounters cancer cells, reovirus invades and produces thousands of copies of itself, causing the cell to burst. The reovirus selectivity is based on its ability to exploit a pathway specific to cancer cells. Specifically, reovirus only infects cells that possess ras, an activated cancer signaling pathway that operates in about 70% of human cancers. Ras acts as a kind of switch to allow reovirus to invade and destroy the cell. Normal cells keep ras (the name of both a gene and its protein product) in check; cancer cells lose control over Ras, resulting in the uncontrolled growth characteristic of deadly tumors.