Oncolytics Announces Publication of Translational Clinical Trial Results in Science Translational Medicine
News Jun 14, 2012
Oncolytics Biotech Inc. has announced that a paper entitled "Cell Carriage, Delivery, and Selective Replication of an Oncolytic Virus in Tumor in Patients," has been published in the latest issue of the journal Science Translational Medicine (Vol. 4 Issue 138 138ra77).
The paper covers findings from a U.K. translational clinical trial (REO 013) investigating intravenous administration of REOLYSIN in patients with metastatic colorectal cancer prior to surgical resection of liver metastases.
The paper was jointly first-authored by researchers from the Leeds Institute of Molecular Medicine, University of Leeds, UK and The Institute of Cancer Research, London, UK.
The trial was an open-label, non-randomized, single centre study of REOLYSIN given intravenously to patients for five consecutive days in advance of their scheduled operations to remove colorectal cancer metastasis in the liver.
Ten patients were treated with intravenous REOLYSIN at 1x1010 TCID50, one to four weeks prior to planned surgery. After surgery, the tumor and surrounding liver tissue were assessed for viral status and anti-tumor effects.
The researchers demonstrated that even though all the treated patients had preexisting immunity to the virus, intravenously administered reovirus could still specifically target and infect metastatic liver tumors in 90% of the patients.
The researchers were able to determine that reovirus was able to evade these neutralizing effects of the immune system by binding to specific blood cells that would in turn deliver the virus to the tumor.
Analysis of surgical specimens demonstrated greater, preferential expression of reovirus protein in malignant cells compared to either tumor stroma or surrounding normal liver tissue.
There was evidence of viral factories within tumor and recovery of replicating virus from tumor (but not normal liver) in all four patients from whom fresh tissue was available.
This is the first time that researchers have been able to demonstrate in patients treated with intravenously delivered oncolytic virus, that a virus could cloak itself from neutralizing antibodies after systemic administration through blood cell carriage and specifically target tumor tissue.
"These are key findings that directly further our understanding of how REOLYSIN interacts with the human immune system and retains its cytotoxicity in the body following intravenous administration," said Dr. Brad Thompson, President and CEO of Oncolytics.
Dr. Thompson continued, "It also highlights the reovirus' unique ability to target cancer cells, and create viral factories within tumor cells, without harming normal, healthy tissue."
"We believe this trial is a key step forward for virotherapy," said Dr. Alan Melcher, Professor of Oncology and Biotherapy at the University of Leeds, UK.
Dr. Melcher continued, "For the first time it shows in patients that intravenously injected reovirus selectively targets cancer, but not normal tissue, for replication and tumor cell killing. It also shows that even when anti-viral antibodies are present in the circulation, the virus can evade neutralization by "hitch-hiking" on blood cells to reach its tumor target."
A new study has identified a drug that potentially could make a common type of immunotherapy for cancer even more effective. The study in laboratory mice found that the drug dasatinib, which is FDA-approved to treat certain types of leukemia, greatly enhances responses to a form of immunotherapy that is used against a wide range of other cancers.